Antidepressant

Antidepressants are medications used to treat major depressive disorder, some anxiety disorders, some chronic pain conditions, and to help manage some addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, headaches, and sexual dysfunction. Most types of antidepressants are typically safe to take, but may cause increased thoughts of suicide when taken by children, adolescents, and young adults. A discontinuation syndrome can occur after stopping any antidepressant which resembles recurrent depression.

Some reviews of antidepressants for depression in adults find benefit while others do not. Evidence of benefit in children and adolescents is unclear. There is debate in the medical community about how much of the observed effects of antidepressants can be attributed to the placebo effect.

Medical uses
Antidepressants are used to treat major depressive disorder and of other conditions, including some anxiety disorders, some chronic pain conditions, and to help manage some addictions. Antidepressants are often used in combinations with one another.

Major depressive disorder
The UK National Institute for Health and Care Excellence (NICE) 2009 guidelines indicate that antidepressants should not be routinely used for the initial treatment of mild depression, because the risk-benefit ratio is poor. The guidelines recommended that antidepressant treatment be considered for:
 People with a history of moderate or severe depression,
 Those with mild depression that has been present for a long period,
 As a second-line treatment for mild depression that persists after other interventions,
 As a first-line treatment for moderate or severe depression.

The guidelines further note that antidepressant treatment should be used in combination with psychosocial interventions in most cases, should be continued for at least six months to reduce the risk of relapse, and that SSRIs are typically better tolerated than other antidepressants.

American Psychiatric Association treatment guidelines recommend that initial treatment should be individually tailored based on factors that include severity of symptoms, co-existing disorders, prior treatment experience, and the person's preference. Options may include pharmacotherapy, psychotherapy, electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or light therapy. They recommended antidepressant medication as an initial treatment choice in people with mild, moderate, or severe major depression, that should be given to all people with severe depression unless ECT is planned.

Some reviews of antidepressants in adults with depression find benefits  while others do not.

Anxiety disorders

Generalized anxiety disorder
Antidepressants are recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of generalized anxiety disorder (GAD) that has failed to respond to conservative measures such as education and self-help activities. GAD is a common disorder of which the central feature is excessive worry about a number of different events. Key symptoms include excessive anxiety about multiple events and issues, and difficulty controlling worrisome thoughts that persists for at least 6 months.

Antidepressants provide a modest-to-moderate reduction in anxiety in GAD. The efficacy of different antidepressants is similar.

Social anxiety disorder

Some antidepressants are used as a treatment for social anxiety disorder, but their efficacy is not entirely convincing, as only a small proportion of antidepressants showed some efficacy for this condition. Paroxetine was the first drug to be FDA-approved for this disorder. Its efficacy is considered beneficial, although not everyone responds favorably to the drug. Sertraline and fluvoxamine extended release were later approved for it as well, while escitalopram is used off-label with acceptable efficacy. However, there isn't enough evidence to support citalopram for treating social phobia, and fluoxetine was no better than placebo in clinical trials. SSRIs are used as a first-line treatment for social anxiety, but they don't work for everyone. One alternative would be venlafaxine, which is a SNRI. It showed benefits for social phobia in five clinical trials against placebo, while the other SNRIs are not considered particularly useful for this disorder as many of them didn't undergo testing for it. As of now, it is unclear if duloxetine and desvenlafaxine can provide benefits for social anxiety sufferers. However, another class of antidepressants called MAOIs are considered effective for social anxiety, but they come with many unwanted side effects and are rarely used. Phenelzine was shown to be a good treatment option, but its use is limited by dietary restrictions. Moclobemide is a RIMA and showed mixed results but still got approval in some European countries for social anxiety disorder. TCA antidepressants, such as clomipramine and imipramine, are not considered effective for this anxiety disorder in particular. This leaves out SSRIs such as paroxetine, sertraline and fluvoxamine CR as acceptable and tolerated treatment options for this disorder.

Obsessive–compulsive disorder
SSRIs are a second-line treatment of adult obsessive–compulsive disorder (OCD) with mild functional impairment and as first-line treatment for those with moderate or severe impairment. In children, SSRIs are considered as a second-line therapy in those with moderate-to-severe impairment, with close monitoring for psychiatric adverse effects. SSRIs appear useful for OCD, at least in the short term. Efficacy has been demonstrated both in short-term treatment trials of 6 to 24 weeks and in discontinuation trials of 28 to 52 weeks duration. Clomipramine, a TCA drug, is considered effective and useful for OCD, however it is used as a second line treatment because it is less well tolerated than the SSRIs. Despite this, it has not shown superiority to fluvoxamine in trials. All SSRIs can be used effectively for OCD, and in some cases, SNRIs can also be tried even though none of them is approved specifically for OCD.  However, even with all these treatment options, many people remain symptomatic after initiating the medication, and less than half of them do achieve remission.

Post traumatic stress disorder
Antidepressants are one of the treatment options for PTSD, however their efficacy is not well established. Two antidepressants are FDA approved for it, paroxetine and sertraline, they belong to the serotonin reuptake inhibitors class. Paroxetine has slightly higher response and remission rates than sertraline for this condition, however both drugs are not considered very helpful for every person that takes them. Fluoxetine and venlafaxine are used off label, with fluoxetine producing unsatisfactory mixed results and venlafaxine, while having a response rates of 78%, which is significantly higher than what paroxetine and sertraline achieved, but it did not address all the symptoms of ptsd like the two drugs did, which is in part due to the fact the venlafaxine is an SNRI, this class of drugs inhibit the reuptake of norepinephrine too, this could cause some anxiety in some people. Fluvoxamine, escitalopram and citalopram were not well tested in this disorder. MAOIs, while some of them may be helpful, are not used much because of their unwanted side effects. This leaves paroxetine and sertraline as acceptable treatment options for some people, although more effective antidepressants are needed.

Panic disorder

Panic disorder is relatively treated well with medications compared with other disorders, several classes of antidepressants have shown efficacy for this disorder, however SSRIs and SNRIs are used first-line. Paroxetine, sertraline, fluoxetine are FDA approved for panic disorder, although fluvoxamine, escitalopram and citalopram are considered effective for it. The SNRI venlafaxine is also approved for this condition. Unlike with social anxiety and PTSD, some TCAs antidepressants, like clomipramine and imipramine, have shown efficacy for panic disorder. Moreover, the MAOI phenelzine is considered useful too. Panic disorder has many drugs for its treatment, however, the starting dose must be lower than the one used for major depressive disorder because people, in the initiation of treatment, have reported an increase in anxiety as a result of starting the medication. In conclusion, while panic disorder's treatment options seem acceptable and useful for this condition, many people are still symptomatic after treatment with residual symptoms.

Eating disorders
Antidepressants are recommended as an alternative or additional first step to self-help programs in the treatment of bulimia nervosa. SSRIs (fluoxetine in particular) are preferred over other antidepressants due to their acceptability, tolerability, and superior reduction of symptoms in short-term trials. Long-term efficacy remains poorly characterized. Bupropion is not recommended for the treatment of eating disorders due to an increased risk of seizure.

Similar recommendations apply to binge eating disorder. SSRIs provide short-term reductions in binge eating behavior, but have not been associated with significant weight loss.

Clinical trials have generated mostly negative results for the use of SSRIs in the treatment of anorexia nervosa. Treatment guidelines from the National Institute of Health and Care Excellence recommend against the use of SSRIs in this disorder. Those from the American Psychiatric Association note that SSRIs confer no advantage regarding weight gain, but that they may be used for the treatment of co-existing depressive, anxiety, or obsessive–compulsive disorders.

Pain

Fibromyalgia

A 2012 meta-analysis concluded that antidepressants treatment favorably affects pain, health-related quality of life, depression, and sleep in fibromyalgia syndrome. Tricyclics appear to be the most effective class, with moderate effects on pain and sleep and small effects on fatigue and health-related quality of life. The fraction of people experiencing a 30% pain reduction on tricyclics was 48% versus 28% for placebo. For SSRIs and SNRIs the fraction of people experiencing a 30% pain reduction was 36% (20% in the placebo comparator arms) and 42% (32% in the corresponding placebo comparator arms). Discontinuation of treatment due to side effects was common. Antidepressants including amitriptyline, fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole are recommended by the European League Against Rheumatism (EULAR) for the treatment of fibromyalgia based on "limited evidence".

Neuropathic pain

A 2014 meta-analysis from the Cochrane Collaboration found the antidepressant duloxetine to be effective for the treatment of pain resulting from diabetic neuropathy. The same group reviewed data for amitriptyline in the treatment of neuropathic pain and found limited useful randomized clinical trial data. They concluded that the long history of successful use in the community for the treatment of fibromyalgia and neuropathic pain justified its continued use. The group was concerned about the potential for overestimating the amount of pain relief provided by amitriptyline, and highlighted that only a small number of people will experience significant pain relief by taking this medication.

Other
Antidepressants may be modestly helpful for treating people who both have depression and alcohol dependence, however the evidence supporting this association of low quality. Buproprion is used to help people stop smoking. Antidepressants may be used to relieve pain in people with active rheumatoid arthritis however, further research is required.

Limitations and strategies

Between 30% and 50% of individuals treated with a given antidepressant do not show a response. Approximately one-third of people achieve a full remission, one-third experience a response and one-third are nonresponders. Partial remission is characterized by the presence of poorly defined residual symptoms. These symptoms typically include depressed mood, anxiety, sleep disturbance, fatigue and diminished interest or pleasure. It is currently unclear which factors predict partial remission. However, it is clear that residual symptoms are powerful predictors of relapse, with relapse rates 3–6 times higher in people with residual symptoms than in those who experience full remission. In addition, antidepressant drugs tend to lose efficacy over the course of treatment. According to data from the Centers for Disease Control and Prevention, less than one-third of Americans taking one antidepressant medication have seen a mental health professional in the previous year. A number of strategies are used in clinical practice to try to overcome these limits and variations. They include switching medication, augmentation, and combination.

Switching antidepressants

The American Psychiatric Association 2000 Practice Guideline advises that where no response is achieved following six to eight weeks of treatment with an antidepressant, to switch to an antidepressant in the same class, then to a different class of antidepressant.  A 2006 meta-analysis review found wide variation in the findings of prior studies; for people who had failed to respond to an SSRI antidepressant, between 12% and 86% showed a response to a new drug. However, the more antidepressants an individual had already tried, the less likely they were to benefit from a new antidepressant trial. However, a later meta-analysis found no difference between switching to a new drug and staying on the old medication; although 34% of treatment resistant people responded when switched to the new drug, 40% responded without being switched.

Augmentation and combination

For a partial response, the American Psychiatric Association guidelines suggest augmentation, or adding a drug from a different class. These include lithium and thyroid augmentation, dopamine agonists, sex steroids, NRIs, glucocorticoid-specific agents, or the newer anticonvulsants.

A combination strategy involves adding another antidepressant, usually from a different class so as to have effect on other mechanisms. Although this may be used in clinical practice, there is little evidence for the relative efficacy or adverse effects of this strategy. Other tests conducted include the use of psychostimulants as an augmentation therapy. Several studies have shown the efficacy of combining modafinil for treatment-resistant people. It has been used to help combat SSRI-associated fatigue.

Long-term use

The effects of antidepressants typically do not continue once the course of medication ends. This results in a high rate of relapse. A 2003 meta-analysis found that 18% of people who had responded to an antidepressant relapsed while still taking it, compared to 41% whose antidepressant was switched for a placebo.

A gradual loss of therapeutic benefit occurs in a minority of people during the course of treatment. A strategy involving the use of pharmacotherapy in the treatment of the acute episode, followed by psychotherapy in its residual phase, has been suggested by some studies.

Adverse effects
Difficulty tolerating adverse effects is the most common reason for antidepressant discontinuation.

Almost any medication involved with serotonin regulation has the potential to cause serotonin toxicity (also known as serotonin syndrome) — an excess of serotonin that can induce mania, restlessness, agitation, emotional lability, insomnia and confusion as its primary symptoms. Although the condition is serious, it is not particularly common, generally only appearing at high doses or while on other medications. Assuming proper medical intervention has been taken (within about 24 hours) it is rarely fatal. Antidepressants appear to increase the risk of diabetes by about 1.3 fold.

MAOIs tend to have pronounced (sometimes fatal) interactions with a wide variety of medications and over-the-counter drugs. If taken with foods that contain very high levels of tyramine (e.g., mature cheese, cured meats, or yeast extracts), they may cause a potentially lethal hypertensive crisis. At lower doses, the person may only experience a headache due to an increase in blood pressure.

In response to these adverse effects, a different type of MAOI has been developed: the reversible inhibitor of monoamine oxidase A (RIMA) class of drugs. Their primary advantage is that they do not require the person to follow a special diet, while being purportedly effective as SSRIs and tricyclics in treating depressive disorders.

Pregnancy

SSRI use in pregnancy has been associated with a variety of risks with varying degrees of proof of causation. As depression is independently associated with negative pregnancy outcomes, determining the extent to which observed associations between antidepressant use and specific adverse outcomes reflects a causative relationship has been difficult in some cases. In other cases, the attribution of adverse outcomes to antidepressant exposure seems fairly clear.

SSRI use in pregnancy is associated with an increased risk of spontaneous abortion of about 1.7-fold, and is associated with preterm birth and low birth weight.

A systematic review of the risk of major birth defects in antidepressant-exposed pregnancies found a small increase (3% to 24%) in the risk of major malformations and a risk of cardiovascular birth defects that did not differ from non-exposed pregnancies. A study of fluoxetine-exposed pregnancies found a 12% increase in the risk of major malformations that just missed statistical significance. Other studies have found an increased risk of cardiovascular birth defects among depressed mothers not undergoing SSRI treatment, suggesting the possibility of ascertainment bias, e.g. that worried mothers may pursue more aggressive testing of their infants. Another study found no increase in cardiovascular birth defects and a 27% increased risk of major malformations in SSRI exposed pregnancies. The FDA advises for the risk of birth defects with the use of paroxetine and the MAOI should be avoided.

A 2013 systematic review and meta-analysis found that antidepressant use during pregnancy was statistically significantly associated with some pregnancy outcomes, such as gestational age and preterm birth, but not with other outcomes. The same review cautioned that because differences between the exposed and unexposed groups were small, it was doubtful whether they were clinically significant.

A neonate (infant less than 28 days old) may experience a withdrawal syndrome from abrupt discontinuation of the antidepressant at birth. Antidepressants have been shown to be present in varying amounts in breast milk, but their effects on infants are currently unknown.

Moreover, SSRIs inhibit nitric oxide synthesis, which plays an important role in setting vascular tone. Several studies have pointed to an increased risk of prematurity associated with SSRI use, and this association may be due to an increase risk of pre-eclampsia of pregnancy.

Antidepressant-induced mania
Another possible problem with antidepressants is the chance of antidepressant-induced mania or hypomania in people with or without a diagnosis of bipolar disorder. Many cases of bipolar depression are very similar to those of unipolar depression. Therefore, the person can be misdiagnosed with unipolar depression and be given antidepressants. Studies have shown that antidepressant-induced mania can occur in 20–40% of people with bipolar. For bipolar depression, antidepressants (most frequently SSRIs) can exacerbate or trigger symptoms of hypomania and mania.

Suicide

Studies have shown that the use of antidepressants is correlated with an increased risk of suicidal behavior and thinking (suicidality) in those aged under 25. This problem has been serious enough to warrant government intervention by the US Food and Drug Administration (FDA) to warn of the increased risk of suicidality during antidepressant treatment. According to the FDA, the heightened risk of suicidality occurs within the first one to two months of treatment. The National Institute for Health and Care Excellence (NICE) places the excess risk in the "early stages of treatment". A meta-analysis suggests that the relationship between antidepressant use and suicidal behavior or thoughts is age-dependent. Compared with placebo, the use of antidepressants is associated with an increase in suicidal behavior or thoughts among those 25 or younger (OR=1.62). There is no effect or possibly a mild protective effect among those aged 25 to 64 (OR=0.79). Antidepressant treatment has a protective effect against suicidality among those aged 65 and over (OR=0.37).

Sexual

Sexual side effects are also common with SSRIs, such as loss of sexual drive, failure to reach orgasm, and erectile dysfunction. Although usually reversible, these sexual side-effects can, in rare cases, continue after the drug has been completely withdrawn.

In a study of 1022 outpatients, overall sexual dysfunction with all antidepressants averaged 59.1% with SSRI values between 57% and 73%, mirtazapine 24%, nefazodone 8%, amineptine 7% and moclobemide 4%. Moclobemide, a selective reversible MAO-A inhibitor, does not cause sexual dysfunction, and can actually lead to an improvement in all aspects of sexual function.

Biochemical mechanisms suggested as causative include increased serotonin, particularly affecting 5-HT2 and 5-HT3 receptors; decreased dopamine; decreased norepinephrine; blockade of cholinergic and α1adrenergic receptors; inhibition of nitric oxide synthetase; and elevation of prolactin levels. Mirtazapine is reported to have fewer sexual side effects, most likely because it antagonizes 5-HT2 and 5-HT3 receptors and may, in some cases, reverse sexual dysfunction induced by SSRIs by the same mechanism.

Bupropion, a weak NDRI and nicotinic antagonist, may be useful in treating reduced libido as a result of SSRI treatment.

Changes in weight
Changes in appetite or weight are common among antidepressants, but are largely drug-dependent and related to which neurotransmitters they affect. Mirtazapine and paroxetine, for example, may be associated with weight gain and/or increased appetite, while others (such as bupropion and venlafaxine) achieve the opposite effect.

The antihistaminic properties of certain TCA- and TeCA-class antidepressants have been shown to contribute to the common side effects of increased appetite and weight gain associated with these classes of medication.

Discontinuation syndrome

Antidepressant discontinuation syndrome, also called antidepressant withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of antidepressant medication. The symptoms may include flu-like symptoms, trouble sleeping, nausea, poor balance, sensory changes, and anxiety. The problem usually begins within three days and may last for several months. Rarely psychosis may occur.

A discontinuation syndrome can occur after stopping any antidepressant including selective serotonin re-uptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs). The risk is greater among those who have taken the medication for longer and when the medication in question has a short half-life. The underlying reason for its occurrence is unclear. The diagnosis is based on the symptoms.

Methods of prevention include gradually decreasing the dose among those who wish to stop, though it is possible for symptoms to occur with tapering. Treatment may include restarting the medication and slowly decreasing the dose. People may also be switched to the long acting antidepressant fluoxetine which can then be gradually decreased.

Approximately 20–50% of people who suddenly stop an antidepressant develop an antidepressant discontinuation syndrome. The condition is generally not serious. Though about half of people with symptoms describe them as severe. Some restart antidepressants due to the severity of the symptoms.

Emotional blunting
SSRIs appear to cause emotional blunting, or numbness in some people who take them. This is a reduction in extremes of emotion, both positive and negative. While the person may feel less depressed, they may also feel less happiness or empathy. This may be cause for a dose reduction or medication change. The mechanism is unknown.

Pharmacology

The earliest and probably most widely accepted scientific theory of antidepressant action is the monoamine hypothesis (which can be traced back to the 1950s), which states that depression is due to an imbalance (most often a deficiency) of the monoamine neurotransmitters (namely serotonin, norepinephrine and dopamine). It was originally proposed based on the observation that certain hydrazine anti-tuberculosis agents produce antidepressant effects, which was later linked to their inhibitory effects on monoamine oxidase, the enzyme that catalyses the breakdown of the monoamine neurotransmitters. All currently marketed antidepressants have the monoamine hypothesis as their theoretical basis, with the possible exception of agomelatine which acts on a dual melatonergic-serotonergic pathway. Despite the success of the monoamine hypothesis it has a number of limitations: for one, all monoaminergic antidepressants have a delayed onset of action of at least a week; and secondly, there are a sizeable portion (>40%) of depressed patients that do not adequately respond to monoaminergic antidepressants. A number of alternative hypotheses have been proposed, including the glutamate, neurogenic, epigenetic, cortisol hypersecretion and inflammatory hypotheses.

Types

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are believed to increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption into the presynaptic cell, increasing the level of serotonin in the synaptic cleft available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, with pure SSRIs having only weak affinity for the norepinephrine and dopamine transporters.

SSRIs are the most widely prescribed antidepressants in many countries. The efficacy of SSRIs in mild or moderate cases of depression has been disputed.

Serotonin–norepinephrine reuptake inhibitors

Serotonin–norepinephrine reuptake inhibitors (SNRIs) are potent inhibitors of the reuptake of serotonin and norepinephrine. These neurotransmitters are known to play an important role in mood. SNRIs can be contrasted with the more widely used selective serotonin reuptake inhibitors (SSRIs), which act mostly upon serotonin alone.

The human serotonin transporter (SERT) and norepinephrine transporter (NET) are membrane proteins that are responsible for the reuptake of serotonin and norepinephrine. Balanced dual inhibition of monoamine reuptake can possibly offer advantages over other antidepressants drugs by treating a wider range of symptoms.

SNRIs are sometimes also used to treat anxiety disorders, obsessive–compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), chronic neuropathic pain, and fibromyalgia syndrome (FMS), and for the relief of menopausal symptoms.

Serotonin modulators and stimulators

Serotonin modulator and stimulators (SMSs), sometimes referred to more simply as "serotonin modulators", are a type of drug with a multimodal action specific to the serotonin neurotransmitter system. To be precise, SMSs simultaneously modulate one or more serotonin receptors and inhibit the reuptake of serotonin. The term was coined in reference to the mechanism of action of the serotonergic antidepressant vortioxetine, which acts as a serotonin reuptake inhibitor (SRI), partial agonist of the 5-HT1A receptor, and antagonist of the 5-HT3 and 5-HT7 receptors. However, it can also technically be applied to vilazodone, which is an antidepressant as well and acts as an SRI and 5-HT1A receptor partial agonist.

An alternative term is serotonin partial agonist/reuptake inhibitor (SPARI), which can be applied only to vilazodone.

Serotonin antagonists and reuptake inhibitors

Serotonin antagonist and reuptake inhibitors (SARIs) while mainly used as antidepressants, are also anxiolytics and hypnotics. They act by antagonizing serotonin receptors such as 5-HT2A and inhibiting the reuptake of serotonin, norepinephrine, and/or dopamine. Additionally, most also act as α1-adrenergic receptor antagonists. The majority of the currently marketed SARIs belong to the phenylpiperazine class of compounds. They include trazodone and nefazodone.

Norepinephrine reuptake inhibitors

Norepinephrine reuptake inhibitors (NRIs or NERIs) are a type of drug that acts as a reuptake inhibitor for the neurotransmitter norepinephrine (noradrenaline) by blocking the action of the norepinephrine transporter (NET). This in turn leads to increased extracellular concentrations of norepinephrine.

NRIs are commonly used in the treatment of conditions like ADHD and narcolepsy due to their psychostimulant effects and in obesity due to their appetite suppressant effects. They are also frequently used as antidepressants for the treatment of major depressive disorder, anxiety and panic disorder. Additionally, many drugs of abuse such as cocaine and methylphenidate possess NRI activity, though it is important to mention that NRIs without combined dopamine reuptake inhibitor (DRI) properties are not significantly rewarding and hence are considered to have a negligible abuse potential. However, norepinephrine has been implicated as acting synergistically with dopamine when actions on the two neurotransmitters are combined (e.g., in the case of NDRIs) to produce rewarding effects in psychostimulant drugs of abuse.

Norepinephrine-dopamine reuptake inhibitors

The only drug used of this class for depression is bupropion.

Tricyclic antidepressants
The majority of the tricyclic antidepressants (TCAs) act primarily as serotonin–norepinephrine reuptake inhibitors (SNRIs) by blocking the serotonin transporter (SERT) and the norepinephrine transporter (NET), respectively, which results in an elevation of the synaptic concentrations of these neurotransmitters, and therefore an enhancement of neurotransmission. Notably, with the sole exception of amineptine, the TCAs have negligible affinity for the dopamine transporter (DAT), and therefore have no efficacy as dopamine reuptake inhibitors (DRIs).

Although TCAs are sometimes prescribed for depressive disorders, they have been largely replaced in clinical use in most parts of the world by newer antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs) and norepinephrine reuptake inhibitors (NRIs). Adverse effects have been found to be of a similar level between TCAs and SSRIs.

Tetracyclic antidepressants

Tetracyclic antidepressants (TeCAs) are a class of antidepressants that were first introduced in the 1970s. They are named after their chemical structure, which contains four rings of atoms, and are closely related to the tricyclic antidepressants (TCAs), which contain three rings of atoms.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders.

Because of potentially lethal dietary and drug interactions, monoamine oxidase inhibitors have historically been reserved as a last line of treatment, used only when other classes of antidepressant drugs (for example selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.

MAOIs have been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, and post-traumatic stress disorder, as well as borderline personality disorder. MAOIs appear to be particularly effective in the management of bipolar depression according to a retrospective-analysis. There are reports of MAOI efficacy in obsessive–compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.

MAOIs can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (therefore affecting dopaminergic neurons), as well as providing an alternative for migraine prophylaxis. Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety disorders.

NMDA receptor antagonists
NMDA receptor antagonists like ketamine and esketamine are rapid-acting antidepressants and seem to work via blockade of the ionotropic glutamate NMDA receptor.

Others

See the list of antidepressants and management of depression for other drugs which are not specifically characterized.

Adjuncts
Adjunct medications are an umbrella category of substances that increase the potency or "enhance" antidepressants. They work by affecting variables very close to the antidepressant, sometimes affecting a completely different mechanism of action. This may be attempted when depression treatments have not been successful in the past.

Common types of adjunct medication techniques generally fall into the following categories:

 Two or more antidepressants taken together
 From the same class (affecting the same area of the brain, often at a much higher level)
 From different classes (affecting multiple parts of the brain not covered simultaneously by either drug alone)
 An antipsychotic combined with an antidepressant, particularly atypical antipsychotics such as aripiprazole (Abilify), quetiapine (Seroquel), olanzapine (Zyprexa), and risperidone (Risperdal).
It is unknown if undergoing psychological therapy at the same time as taking anti-depressants enhances the anti-depressive effect of the medication.

Less common adjunct medication
Lithium has been used to augment antidepressant therapy in those who have failed to respond to antidepressants alone. Furthermore, lithium dramatically decreases the suicide risk in recurrent depression. There is some evidence for the addition of a thyroid hormone, triiodothyronine, in patients with normal thyroid function.

Psychopharmacologists have also tried adding a stimulant, in particular, d-amphetamine. However, the use of stimulants in cases of treatment-resistant depression is relatively controversial. A review article published in 2007 found psychostimulants may be effective in treatment-resistant depression with concomitant antidepressant therapy, but a more certain conclusion could not be drawn due to substantial deficiencies in the studies available for consideration, and the somewhat contradictory nature of their results.

History

Before the 1950s, opioids and amphetamines were commonly used as antidepressants. Their use was later restricted due to their addictive nature and side effects. Extracts from the herb St John's wort have been used as a "nerve tonic" to alleviate depression.

Isoniazid, iproniazid, and imipramine
In 1951, Irving Selikoff and , working out of Sea View Hospital on Staten Island, began clinical trials on two new anti-tuberculosis agents developed by Hoffman-LaRoche, isoniazid and iproniazid. Only patients with a poor prognosis were initially treated; nevertheless, their condition improved dramatically. Selikoff and Robitzek noted "a subtle general stimulation ... the patients exhibited renewed vigor and indeed this occasionally served to introduce disciplinary problems." The promise of a cure for tuberculosis in the Sea View Hospital trials was excitedly discussed in the mainstream press.

In 1952, learning of the stimulating side effects of isoniazid, the Cincinnati psychiatrist Max Lurie tried it on his patients. In the following year, he and Harry Salzer reported that isoniazid improved depression in two-thirds of their patients and coined the term antidepressant to refer to its action. A similar incident took place in Paris, where Jean Delay, head of psychiatry at Sainte-Anne Hospital, heard of this effect from his pulmonology colleagues at Cochin Hospital. In 1952 (before Lurie and Salzer), Delay, with the resident , reported the positive effect of isoniazid on depressed patients. The mode of antidepressant action of isoniazid is still unclear. It is speculated that its effect is due to the inhibition of diamine oxidase, coupled with a weak inhibition of monoamine oxidase A.

Selikoff and Robitzek also experimented with another anti-tuberculosis drug, iproniazid; it showed a greater psychostimulant effect, but more pronounced toxicity. Later, Jackson Smith, Gordon Kamman, George E. Crane, and Frank Ayd, described the psychiatric applications of iproniazid. Ernst Zeller found iproniazid to be a potent monoamine oxidase inhibitor. Nevertheless, iproniazid remained relatively obscure until Nathan S. Kline, the influential head of research at Rockland State Hospital, began to popularize it in the medical and popular press as a "psychic energizer". Roche put a significant marketing effort behind iproniazid. Its sales grew until it was recalled in 1961, due to reports of lethal hepatotoxicity.

The antidepressant effect of a tricyclic, a three ringed compound, was first discovered in 1957 by Roland Kuhn in a Swiss psychiatric hospital. Antihistamine derivatives were used to treat surgical shock and later as neuroleptics. Although in 1955 reserpine was shown to be more effective than placebo in alleviating anxious depression, neuroleptics were being developed as sedatives and antipsychotics.

Attempting to improve the effectiveness of chlorpromazine, Kuhn in conjunction with the Geigy Pharmaceutical Company discovered the compound "G 22355", later renamed imipramine. Imipramine had a beneficial effect in patients with depression who showed mental and motor retardation. Kuhn described his new compound as a "thymoleptic" "taking hold of the emotions," in contrast with neuroleptics, "taking hold of the nerves" in 1955–56. These gradually became established, resulting in the patent and manufacture in the US in 1951 by Häfliger and SchinderA.

Second generation antidepressants

Antidepressants became prescription drugs in the 1950s. It was estimated that no more than 50 to 100 individuals per million suffered from the kind of depression that these new drugs would treat, and pharmaceutical companies were not enthusiastic in marketing for this small market. Sales through the 1960s remained poor compared to the sales of tranquilizers, which were being marketed for different uses. Imipramine remained in common use and numerous successors were introduced. The use of monoamine oxidase inhibitors (MAOI) increased after the development and introduction of "reversible" forms affecting only the MAO-A subtype of inhibitors, making this drug safer to use.

By the 1960s, it was thought that the mode of action of tricyclics was to inhibit norepinephrine reuptake. However, norepinephrine reuptake became associated with stimulating effects. Later tricyclics were thought to affect serotonin as proposed in 1969 by Carlsson and Lindqvist as well as Lapin and Oxenkrug.

Researchers began a process of rational drug design to isolate antihistamine-derived compounds that would selectively target these systems. The first such compound to be patented was zimelidine in 1971, while the first released clinically was indalpine. Fluoxetine was approved for commercial use by the US Food and Drug Administration (FDA) in 1988, becoming the first blockbuster SSRI. Fluoxetine was developed at Eli Lilly and Company in the early 1970s by Bryan Molloy, Klaus Schmiegel, David T. Wong and others. SSRIs became known as "novel antidepressants" along with other newer drugs such as SNRIs and NRIs with various selective effects.

St John's wort fell out of favor in most countries through the 19th and 20th centuries, except in Germany, where Hypericum extracts were eventually licensed, packaged and prescribed. Small-scale efficacy trials were carried out in the 1970s and 1980s, and attention grew in the 1990s following a meta-analysis. It remains an over-the-counter drug (OTC) supplement in most countries. Of concern are lead contaminant; on average, lead levels in women in the United States taking St. John's wort are elevated about 20%.  Research continues to investigate its active component hyperforin, and to further understand its mode of action.

Rapid-acting antidepressants
Esketamine (brand name Spravato), the first rapid-acting antidepressant to be approved for clinical treatment of depression, was introduced for this indication in March 2019 in the United States.

Society and culture

Prescription trends

In the United States, antidepressants were the most commonly prescribed medication in 2013. Of the estimated 16 million "long term" (over 24 months) users, roughly 70 percent are female. As of 2017, about 16.5% of white people in the United States took antidepressants compared with 5.6% of black people in the United States.

In the UK, figures reported in 2010 indicated that the number of antidepressants prescribed by the National Health Service (NHS) almost doubled over a decade. Further analysis published in 2014 showed that number of antidepressants dispensed annually in the community went up by 25 million in the 14 years between 1998 and 2012, rising from 15 million to 40 million. Nearly 50% of this rise occurred in the four years after the 2008 banking crash, during which time the annual increase in prescriptions rose from 6.7% to 8.5%. These sources also suggest that aside from the recession, other factors that may influence changes in prescribing rates may include: improvements in diagnosis, a reduction of the stigma surrounding mental health, broader prescribing trends, GP characteristics, geographical location and housing status. Another factor that may contribute to increasing consumption of antidepressants is the fact that these medications now are used for other conditions including social anxiety and posttraumatic stress disorder.

United States: The most commonly prescribed antidepressants in the US retail market in 2010 were:

Netherlands: In the Netherlands, paroxetine is the most prescribed antidepressant, followed by amitriptyline, citalopram and venlafaxine.

Adherence

As of 2003, worldwide, 30 to 60% of people didn't follow their practitioner's instructions about taking their antidepressants, and as of 2013 in the US, it appeared that around 50% of people did not take their antidepressants as directed by their practitioner.

When people fail to take their antidepressants, there is a greater risk that the drug won't help, that symptoms get worse, that they miss work or are less productive at work, and that the person may be hospitalized. This also increases costs for caring for them.

Social science perspective
Some academics have highlighted the need to examine the use of antidepressants and other medical treatments in cross-cultural terms, due to the fact that various cultures prescribe and observe different manifestations, symptoms, meanings and associations of depression and other medical conditions within their populations. These cross-cultural discrepancies, it has been argued, then have implications on the perceived efficacy and use of antidepressants and other strategies in the treatment of depression in these different cultures. In India, antidepressants are largely seen as tools to combat marginality, promising the individual the ability to reintegrate into society through their use—a view and association not observed in the West.

Environmental impacts
Because most antidepressants function by inhibiting the reuptake of neurotransmitters serotonin, dopamine, and norepinepherine these drugs can interfere with natural neurotransmitter levels in other organisms impacted by indirect exposure. Antidepressants fluoxetine and sertraline have been detected in aquatic organisms residing in effluent dominated streams. The presence of antidepressants in surface waters and aquatic organisms has caused concern because ecotoxicological effects to aquatic organisms due to fluoxetine exposure have been demonstrated.

Coral reef fish have been demonstrated to modulate aggressive behavior through serotonin. Artificially increasing serotonin levels in crustaceans can temporarily reverse social status and turn subordinates into aggressive and territorial dominant males.

Exposure to fluoxetine has been demonstrated to increase serotonergic activity in fish, subsequently reducing aggressive behavior. Perinatal exposure to fluoxetine at relevant environmental concentrations has been shown to lead to significant modifications of memory processing in 1-month-old cuttlefish. This impairment may disadvantage cuttlefish and decrease their survival. Somewhat less than 10% of orally administered fluoxetine is excreted from humans unchanged or as glucuronide.


Jared Kusnitz

Jared Andrew Kusnitz (born November 8, 1988) is an American actor. He has appeared in the films Doll Graveyard (2005), Dance of the Dead (2008), and Prom (2011), and television series such as The Secret Life of the American Teenager, Good Luck Charlie, and  Underemployed.

Early life
Kusnitz was born in Fort Lauderdale, Florida, where he was raised. He is Jewish.

Filmography

Film

Television


Dorge Kouemaha

Dorge Rostand Kouemaha (born 28 June 1983) is a Cameroonian former professional footballer who plays as a forward for Belgian club Sprimont Comblain.

Career
Kouemaha joined Greek side Aris in January 2005 from Victoria United Limbé as actual topscorer of the Cameroonian League. He made his debut for the club in a cup match against Ethnikos Piraeus, scoring the match winner after being brought as a sub in the 59th minute. In August 2005, Kouemaha was transferred to Hungarian side Tatabánya FC. He immediately managed to become a regular scorer for a relatively weak team in the Hungarian league. His 14 league goals for Tatabánya helped him to attract the interest of league leader Debreceni VSC. He finally moved to Debrecen to become their topscorer with 14 league goals in the 2007–08 season.

German 2. Bundesliga outfit MSV Duisburg signed Kouemaha for their 2008–09 campaign. Boosted by his first nomination to the Cameroonian national team, Kouemaha answered the expectations once more by scoring 15 goals in 35 matches. His immediate success in German football led to a €1.2 million move to Belgian club Club Brugge KV for the 2009–10 season. His 16 league goals during that season made him the top goalgetter of the Belgian League. The steady progress in his career broke down with permanent problems with his Achilles tendon in the 2010–11 season which led to a rupture while playing on loan for 1. FC Kaiserslautern in February 2012. Kouemaha celebrated his comeback in the Bundesliga match against Mainz 05 on 27 November 2012 meanwhile playing for Eintracht Frankfurt on loan from Brugge.

In the beginning of 2013, he was loaned to Gaziantepspor having made only two short appearances for Eintracht. After spending two seasons in Turkey, he returned to the Belgian Pro League for Lierse on 16 June 2014, signing a two-year deal.

On 9 January 2016, Kouemaha signed with Iranian club Foolad.


Majak

Majak can refer to

 Mayak (disambiguation)
 Achok Majak, American model
 Majak Daw, an Australian rules footballer playing for the North Melbourne Football Club in the Australian Football League (AFL)
 Mij, Fars, also called Majak, a small town in Iran


Stichic

Poetry made up of lines of the same approximate meter and length, not broken up into stanzas, is called stichic (as opposed to stanzaic, e.g.).  Most poetry from the Old English period is considered stichic. Most English poetry written in blank verse, such as the epic Paradise Lost by John Milton, is stichic. A more contemporary example is Joanna Baillie's "Hay making"


Lucien De Muynck

Lucien De Muynck (born 1 August 1931) is a Belgian middle-distance runner. He competed in the men's 800 metres at the 1952 Summer Olympics.


Gülnar

Gülnar is a district of Mersin Province of Turkey,  south-west of the city of Mersin.

Geography
The town of Gülnar is  inland on a plain high in the Taurus Mountains, attractive countryside known for its vineyards and its green meadows used for summer grazing. Gülnar is a small town  providing high schools and other basic amenities to the surrounding villages.(Town population. 8 357) The road from central Anatolia to Anamur on the Mediterranean coast passes through here, one of the windiest roads imaginable, making Gulnar a remote district indeed.

The land area of Gülnar is  of which  is cultivated,  is forested hillside,  is high meadow, and  is rocky mountains. Much of the cultivated area is vineyards, other important crops are grains and chick peas. The high meadows are used for summer grazing.

History
The area has been occupied since the time of the Hittites, and was later settled by the Assyrians, Persians, Egyptians, the Greeks, the Ancient Romans and Armenians. The people of Gülnar today are descendants of the Turkmen tribes that came here from Central Asia in the 13th century. (Among older generation of Turkmens Gülnar is usually named as Anaypazarı )


Camiguin de Babuyanes

Camiguin de Babuyanes is an active stratovolcano on Camiguin Island, part of the Babuyan Islands group that is located in Luzon Strait, north of the island of Luzon, in the Philippines.  The volcano and the island is within the jurisdiction of the municipality of Calayan, in the province of Cagayan.

Physical features
The well-forested Mount Camiguin or Camiguin de Babuyanes, to distinguish it from Camiguin of Mindanao, has an elevation of  asl, and a base diameter of .  It occupies the SW tip of  long Camiguin Island.

Fumaroles are found on the southwest, west, and east flanks of the volcano and a boiling spring is located near sea level on the western flank of the volcano (magas-asok).

The Philippine Institute of Volcanology and Seismology (PHILVOCS) lists Camiguin de Babuyanes as one of the active volcanoes in the Philippines.

All volcanoes in the Philippines are part of the Pacific ring of fire.

Eruptions
An eruption was recorded around 1857. It was reported as phreatic and possibly partly submarine.

In 1991, there were reports of volcanic activity but instrumental investigations showed no sign of unusual volcanic activity, such as intense fumarolic activity, felt earthquakes, fissuring at the volcano's slopes, or smell of sulphur.

Another report of volcanic unrest was reported in 1993 but an aerial survey of the volcano proved no signs of activity.

Geology
Formation of the island started during the Pliocene era with an andesitic volcano, followed by the subsidiary cones of Minabel to the north and Caanoan in the eastern part of the island.

The southern part of the island consists of three volcanic centers located traversing a SSE-NNW line, Mount Camiguin stratovolcano and the young andesitic lava domes of Mts. Malabsing and Pamoctan.


Microsoft Indic Language Input Tool

Microsoft Indic Language Input Tool is a typing tool (Input Method Editor) for languages written in Indic scripts. It is a virtual keyboard which allows to type Indic text directly in any application without hassle of copying and pasting. It is available for both, online and offline use. It was released in December 2009.

It works on the Dictionary-based Phonetic Transliteration approach. It means whatever you type in Latin characters, it matches that with its dictionary and transliterates it, it also gives suggestions for matching words.


Bert Coan

Elroy Bert Coan III (born July 2, 1940 in Timpson, Texas) is a former American football player.  He is most notable because of his extraordinary speed (9.4 in the 100-yard dash) and size (6'4", 215 lbs) and because he was the central figure in a dispute over the 1960 college football game between the University of Kansas Jayhawks and the University of Missouri Tigers, the second-longest-running rivalry in college football (known as the "Border War").  Coan played for Kansas - and helped the Jayhawks win the 1960 game by a score of 23-7 over Missouri, then-ranked #1.  But later, the Big Eight declared Coan ineligible, due to a recruiting violation by Bud Adams while Coan was still at Texas Christian University (TCU) and forfeited the game to Missouri—thus erasing Missouri's only loss on the field that year.  Missouri counts the 1960 game as a win by forfeit, thus giving it the only undefeated and untied season in school history. The Big Eight also credited the 1960 game to Missouri. However, Kansas (and the NCAA) count the game as a Kansas victory.  Ever since, the two universities have disputed the overall win-loss record in the long-running series.

Coan went on to play in 72 games in seven seasons in the American Football League; the first season with the San Diego Chargers, and the rest with the Kansas City Chiefs.

External links


Colton Harris Moore

Colton Harris Moore (born March 22, 1991) is an American former fugitive. He was charged with the theft of hundreds of thousands of dollars in property, including several small aircraft, boats, and multiple cars, all committed while still a teenager.

He fled to the Bahamas on July 4, 2010, allegedly in a plane stolen from Bloomington, Indiana. He was indicted on July 6, 2010, by a U.S. Federal Court in Seattle, Washington, on charges of transporting another stolen aircraft in that state. Moore, still only 19, was arrested in Harbour Island, Bahamas, on July 11, 2010, after police shot out the engine of the boat in which he was attempting to flee. Two days later, he was extradited from Nassau, Bahamas, to Miami, Florida, and transferred on July 21 to the Federal Detention Center, SeaTac in Washington. On December 16, 2011, Moore was sentenced to more than seven years in prison for dozens of consolidated charges brought against him from three different counties. On January 27, 2012, he was sentenced to six and a half years for related federal crimes.

He became known as the "Barefoot Bandit" by reportedly committing some of his crimes barefoot, once leaving behind 39 chalk footprints and the word "c'ya!". Despite the widely reported nickname, officials said that he more often wore shoes.

On September 28, 2016, Moore left prison on parole.

Background
Moore was born in Mount Vernon, Washington and grew up in his mother's house in Camano Island. Neighbors said they made several calls to Child Protective Services, believing he was neglected or abused. His father, Gordon Moore, used drugs and was in prison while Colton was a toddler. When Colton was twelve years old, his father walked out after an argument at a family barbecue. According to his mother, Pamela Kohler, his stepfather died when he was about seven years old, and from the time Colton was in the first grade, she knew there was "something off about him" – "sort of a disconnection". He wouldn't listen to his teachers, started altercations at school, and would sometimes deliberately break things around the house, Kohler said. According to a court-ordered psychiatric evaluation, Moore said that his mother drank and became mean, breaking his possessions.

He started living in the wild at the age of seven, and would break into vacation homes in the area, stealing blankets, food and water before disappearing into the forest for days. His first conviction for stolen property came at age 12, and by the time he was 13, he had three more. He has been diagnosed with depression, attention deficit disorder and intermittent explosive disorder. Each conviction brought a 10-day stay in a detention center, or community service. His mother once said, "Every time he had anything any good, everyone thought he stole it. What does that do to a kid?" In 2003, police found a neighbor's camcorder in his home. Never before sentenced to more than a month, he fled a three-year sentence by walking out of a halfway house in April 2008.

Suspected offenses

Moore is suspected of being responsible for approximately 100 thefts in Washington, Idaho, and Canada, including bicycles, automobiles, light aircraft, and speedboats.  It is believed that he learned how to fly small planes by reading aircraft manuals, handbooks, watching a "How to fly a small airplane" DVD, and playing flight simulator computer games. One plane he stole was a Cessna 182, FAA registration number N24658, belonging to then KZOK-FM radio personality Bob Rivers, valued at over $150,000. The plane was later recovered from a Yakama Indian Reservation crash site.  Though badly damaged, it was rebuilt and is  in Florida.

According to local sheriffs, Moore would often slip into a home just to soak in a hot bath or steal ice cream from the freezer. While his thefts would escalate to increasing value in cash and property, he initially would steal only what he needed for living in the woods as a survivalist. Once, he allegedly used a homeowner's computer and credit card to order bear mace and a pair of $6,500 night vision goggles.

On May 30 or 31, 2010, police found a handwritten note and $100 at a veterinary clinic in Raymond, Washington, approximately  southwest of Seattle. The note read:

In late June 2010, Moore was suspected of vehicle thefts stretching as far east as Illinois. The trail of suspected thefts attributed to him passes through Idaho, South Dakota, Nebraska, Iowa, and Illinois. Police found a 2008 white Toyota Sequoia in Norfolk, Nebraska, which was reported stolen in Yankton, South Dakota. Later that day, several burglaries were reported at Karl Stefan Memorial Airport, located  south of where the SUV was abandoned. A truck owned by the town of Ottumwa, Iowa, was later recovered in Dallas City, Illinois.  On July 4, 2010, a Cessna 400 single-engine plane was reported stolen from the Bloomington, Indiana, airport. It was later found crashed in the shoreline waters of Great Abaco Island in the Bahamas, again leading to speculation that Moore was responsible. Shortly afterward, there were several break-ins reported across the island. The Royal Bahamas Police Force placed wanted posters across the island that featured the teenager. One bartender claimed to have spotted him in a sports bar on Tuesday, July 6, 2010, stating that he drank a beer and left after five minutes. He says that Moore was wearing a cap over his shaved head and was barefoot.

On July 6, 2010, an indictment was released from a federal judge of the U.S. District Court of Western Washington, which was originally filed in December 2009. This indictment cites Moore for interstate transport of stolen property/airplane theft, related to a plane stolen from Bonners Ferry, Idaho that crashed outside of Granite Falls, Washington. The FBI placed a $10,000 bounty for information leading to his arrest, and federal agents believed that he was responsible for the recent Indiana theft.

Capture

On July 11, 2010, Moore was captured just before dawn at Harbour Island, Bahamas. Local officers picked up his trail in Eleuthera after recovering a 44-foot (13-meter) power boat stolen from a marina on Great Abaco. A police official said the suspect attempted to flee, but police shot out the engine on his stolen boat. Before being arrested, Moore threw his portable computer into the water and put a gun to his head, but the police talked him out of killing himself. He told the police that he intended to go to Cuba to throw authorities off his trail and from there to the Turks and Caicos Islands. His mother had hoped that he would flee to a country that did not have an extradition treaty with the United States.

In March 2011, FBI Special Agent Fred Gutt confirmed the reward fund payout: "The $10,000 bounty money was paid out to people directly involved in (Moore's) capture." The reward money was split among Jordan Sackett, Capt. Ronald Billiot, Capt. Patrick Young, Capt. Ben Johnson and Kenny Strachan, a security guard at the Romora Bay Resort.

Criminal proceedings
Moore pleaded guilty on July 13, 2010, to illegal entry to the Bahamas and illegally landing a plane. He was sentenced to three months in jail or a $300 fine. His mother wired the money to the U.S. Embassy in Nassau, which in turn paid the fine. He was deported the same day via overnight commercial flight, accompanied by Bahamian authorities and United States agents of the FBI to Miami, Florida. On July 14, Moore appeared before U.S. Magistrate Robert Dube to determine his legal representation, which had been hired on his behalf by his mother.

In a hearing on July 16, 2010, in the U.S. District Court of Southern Florida, Judge Dube ruled that Moore would be sent to Washington state to face charges there first because he was arrested under their warrant. Moore waived his right to an extradition hearing. He was held at the Federal Detention Center in Miami until July 21, when he was transferred by the Justice Prisoner and Alien Transportation System to the Federal Detention Center in SeaTac, Washington. He was required to wear handcuffs and leg irons while being transported to Washington. A federal judge at the U.S. District Court of Western Washington in Seattle set a November 15 deadline for prosecutors to have Moore formally indicted by a federal grand jury. However, Moore waived his right to a speedy trial, permitting both the defense and the prosecution more time to prepare for the case. On November 18, 2010, Moore pleaded not guilty in federal court to charges of interstate transportation of a stolen plane, boat and gun, and of being a fugitive in possession of a firearm and of flying a plane without a pilot's license.

On September 30, 2010, Harley Davidson Ironwing, a self-described associate of Moore's burglaries, pleaded guilty to assault and was sentenced to 18 months in prison.

On June 17, 2011, federal prosecutors recommended that Moore be sentenced to six years in prison. Moore pleaded guilty to all seven counts on the federal indictment. The Washington State Court, however, recommended that he be sentenced to 10 years in prison for a break-in and burglary near Granite Falls, Washington.

At sentencing, prosecutors were expected to ask for a term of 9½ years, while Moore's attorneys, John Henry Browne and Emma Scanlan, were expected to ask for a 6 year term, citing psychiatric and mitigation reports describing his bleak childhood.

On December 16, 2011, Moore was sentenced in Island County court to more than seven years in prison. Superior Court Judge Vickie Churchill stated, "This case is a tragedy in many ways, but it's a triumph of the human spirit in other ways." Describing Moore's childhood as a "mind numbing absence of hope," she stated the 20-year-old was genuinely remorseful for his crimes.  Moore has said that he plans to spend his time in prison studying in preparation for applying to college in order to earn a degree in aeronautical engineering.

On January 27, 2012, Judge Richard Jones of Federal District Court in Seattle sentenced Moore to six and a half years in prison for his infamous international crime spree. During sentencing Moore addressed the court and U.S. Judge Richard Jones, saying that it is "no stretch of the imagination to say that I'm lucky to be alive." His federal sentence will be served jointly with state prison time.

Notoriety
Moore became known as the "Barefoot Bandit" or as the "Barefoot Burglar", for reportedly committing some of his crimes while barefoot. In Fall 2009, police found footprints at an airport hangar in Bonners Ferry, Idaho; a Cessna 182 stolen from there crash-landed approximately  to the west near Granite Falls, Washington, after a few unsuccessful attempts to land at the small airport there. Police in the San Juan Islands also found cartoonish, chalk outlines of feet drawn upon the floor of a grocery store that was broken into in February 2010. Moore became an internet sensation with a Facebook fan page drawing about 60,000 members. A local Seattle man started selling T-shirts bearing Moore's picture with the words "Momma Tried". Local people from Camano Island also attempted to vent their frustrations through a song, as well as a blog which included the sale of merchandise and accepted donations to purchase the services of a bounty hunter.

In April 2010, 20th Century Fox purchased the film rights to the book The Barefoot Bandit: The True Tale of Colton Harris-Moore, New American Outlaw, by Bob Friel. Moore's mother has retained celebrity lawyer Yale Lewis to seek control of entertainment interests related to her son. She has also hired John Henry Browne to handle her son's criminal defense. Under a plea deal Moore agreed to forfeit any profits from selling publishing rights to his story.

The Barefoot Bandit Documentary (which premiered at Friday Harbor Film Festival on November 7, 2014, filmmaker Carly Bodmer) explores the childhood and time that Moore spent evading the law. Pam Kohler (Colton's mother), the FBI, lawyer John Henry Browne, and a range of personalities from Moore's hometown to the Bahamas piece together why he did what he did.

A 2014 Canadian documentary about Moore called Fly Colt Fly: Legend of the Barefoot Bandit was made by brothers Adam and Andrew Gray, showing how the mythic story evolved in the media and how Moore became a 21st century outlaw folk hero.

In December 2015, Moore began publishing a blog which has since been taken down. His stated intent was to break his long-standing silence, and to voice his support for presidential candidate Donald Trump.

In July 2016, Moore was released on probation to a halfway house near Seattle. Moore has reportedly secured a job at his defense attorney's Seattle law firm, doing "low-level clerical work". His efforts to raise money via social media to fund flight school training were vetoed by his parole officer, who said any money raised must go toward the $129,000 in restitution that he owes his victims.


Artus (disambiguation)

Artus is a name.

Artus or Arthus may also refer to:

 Artus Court, a building in Gdańsk, Poland
 Artus de Lionne (1655–1713), bishop and French missionary
 Artus Prime, a fictional planet in the Star Wars franchise
 Artus, a 2019 album by German band Schandmaul
 K11 ARTUS, a residential area in Victoria Dockside, Hong Kong


Shift Work

Shift Work are a London-based live electronics band composed of Mark Harris and Johnny Rivo.  Harris was previously a member of Factory Floor.

Shift Work are currently signed to Houndstooth.

Discography

EPs
"Scaled to Fit" 12" (2014), Optimo Music
"Document II" 12" (2015), Houndstooth
"HTH050: Various Artists - Tessellations (2016), Houndstooth


Timothy Szymanski

Timothy Gerard "Tim" Szymanski, a United States Navy Vice Admiral, is deputy commander of United States Special Operations Command. He is the former commander of Naval Special Warfare Command in Coronado, California.

Early life and education
Rear Admiral Szymanski is a native of Wilmington, Delaware. He graduated from the Salesianum School in 1980, where he was a three-year varsity letterman in wrestling and, in 1980,  represented the United States in an international AAU Freestyle wrestling tournament in Tokyo, Japan. He then attended the U.S. Naval Academy Preparatory School from 1980 to 1981, and graduated from the United States Naval Academy in 1985.

He completed a Masters of Joint Campaign Planning and Strategy at Joint Advanced Warfighting School.

Career
After receiving his commission in 1985, Szymanski served in the Surface Warfare community and qualified as a surface warfare officer before transitioning to the SEALs. He volunteered for Basic Underwater Demolition/SEAL training (BUD/S) graduating with Class 161 in 1989.

Szymanski’s Naval Special Warfare (NSW) and operational assignments include platoon and task unit commander at SEAL Delivery Vehicle Team 2. In 1992, Szymanski was assigned to Naval Special Warfare Development Group in Damneck, Va and completed the nine month selection and training course known as green team. He then served as troop and squadron commander with the unit until 1997 and returned as operations officer from 2000 to 2002. He commanded Special Boat Unit 26, SEAL Team 2 from 2002 to 2004, O6-level Joint Task Force in Afghanistan, and Naval Special Warfare Group 2 from 2011 to 2013. He served as deputy commanding general sustainment to Special Operations Joint Task Force-Afghanistan/NATO Special Operations Component Command-Afghanistan.

Szymanski’s previous staff assignments include officer community manager for NSW and enlisted community manager for SEALs, Navy Divers, explosive ordnance disposal technicians, and special warfare combatant craft crewmen. He served on the Joint Staff as the J3 deputy directorate for Special Operations as the Global War on Terror branch chief and as chief staff officer of Pakistan-Afghanistan Coordination Cell.

On 3 August 2016, Szymanski succeeded Rear Admiral Brian L. Losey as Commander, Naval Special Warfare Command. His prior assignment was the assistant commanding general of Joint Special Operations Command at Fort Bragg, North Carolina.

On 19 July 2018, Szymanski was nominated for promotion to vice admiral but his next assignment was not disclosed at the time.

Awards and decorations
Szymanski has received multiple awards and recognitions:

In 2015, Szymanski was inducted into Salesianum School's hall of fame.


William Walaska

William A. Walaska (September 16, 1946 – April 3, 2017) was an American Democratic politician and a member of the Rhode Island Senate who represented District 30 from 2003 to 2017. Walaska served consecutively from January 1995 until January 2003 in the District 17 seat.

Education
Walaska attended Williams College and Dartmouth College, and earned his BA in economics and his MBA from Providence College.

Elections
2012 Walaska was unopposed for the September 11, 2012 Democratic Primary, winning with 882 votes, and won the three-way November 6, 2012 General election with 7,585 votes (61.0%) against Republican nominee Keith Burkitt and Independent candidate Arthur Groh.
1994 When District 17 incumbent Senator Thomas Lynch left the Legislature and left the seat open, Walaska won the September 13, 1994 Democratic Primary and won the November 8, 1994 General election with 4,424 votes (57.7%) against Republican nominee Steven Archer.
1996 Walaska and returning 1994 Republican opponent Steven Archer were both unopposed for their September 10, 1996 primaries, setting up a rematch; Walaska won the November 5, 1996 General election with 5,353 votes (68.9%) against Archer.
1998 Walaska was unopposed for the September 15, 1998 Democratic Primary, winning with 1,475 votes, and won the November 3, 1998 General election with 4,941 votes (73.4%) against Republican nominee Raymond McKay.
2000 Walaska was unopposed for both the September 12, 2000 Democratic Primary, winning with 1,704 votes, and the November 7, 2000 General election, winning with 6,373 votes.
2002 Redistricted to District 30, and with incumbent Democratic Senator Paul Kelly retiring and leaving the seat open, Walaska was unopposed for both the September 10, 2002 Democratic Primary, winning with 1,932 votes, and the November 5, 2002 General election, winning with 7,331 votes.
2004 Walaska was unopposed for the September 14, 2004 Democratic Primary, winning with 512 votes, and won the November 2, 2004 General election with 7,758 votes (69.5%) against Republican nominee Roland Denomme.
2006 Walaska was unopposed for both the September 12, 2006 Democratic Primary, winning with 1,483 votes, and the November 7, 2006 General election, winning with 8,916 votes.
2008 Walaska was unopposed for both the September 9, 2008 Democratic Primary, winning with 1,013 votes, and the November 4, 2008 General election, winning with 9,256 votes.
2010 Walaska was unopposed for the September 23, 2010 Democratic Primary, winning with 1,306 votes, and won the November 2, 2010 General election with 5,545 votes (57.3%) against Republican nominee Armand Lusi.
2016 Walaska was defeated by Jeanine Calkin in the September 13, 2016 Democratic Primary by a 75-vote margin, ending his 22-year career in the Rhode Island Senate

Death
Walaska died on April 3, 2017 of cancer.


Margaret Bannerman

Margaret Bannerman (born Marguerite Grand, December 15, 1896 – June 14, 1976) was a Canadian actress. She is known for her work in the English films The Gay Lord Quex, Lady Audley's Secret and Hindle Wakes. She had a successful career on stage, appearing in revues and light comedy.

Bannerman was born in Toronto, Ontario on December 15, 1896 to parents Charles Grand and Margaret Hurst. She attended Bishop Strachan School in Toronto, then the Mount Saint Vincent Academy in Halifax, Nova Scotia. The family moved to England at the outbreak of World War I.

Grand began her career in English theatre in 1915 in Charlotte's Revue starring Gertrude Lawrence. During the silent age she appeared in several English comedy films. A high point of her acting career was the part of Lady George Graystone in Somerset Maugham's Our Betters, which ran for 548 performances at the Globe Theatre in London, England. A nervous breakdown in 1925 interrupted her acting career. After a year of touring Australia in 1928, she returned to London theatre before moving to the United States in the 1930s. She returned to acting in film in the 1930s, attempting to break into American films. She appeared in films until 1947 and continued in theatre until 1963.

Bannerman performed professionally twice in her hometown, firstly in 1940 in Our Better's at the Royal Alexandra Theatre. She made one final performance in her hometown in November 1963, as Mrs. Higgins in the touring company of My Fair Lady. She then retired to an actor's home in Englewood, New Jersey where she continued her life-long interests in furniture and antiques. Bannerman was married twice, to London producer Anthony Prinsep and actor Pat Somerset.

Selected filmography
 Justice (1917) - Miss Cokeson
 The Gay Lord Quex (1917) - Muriel Eden
 Flames (1917) - Cuckoo
 Mary Girl (1917) - Countess Folkington
 Hindle Wakes (1918) - Beatrice Farrar
 Goodbye (1918) - Florence Tempest
 Her Secret (1919) - Margaret Henderson
 Lady Audley's Secret (1920) - Lady Audley
 The Grass Orphan (1922) - Mrs. St. John
 Two White Arms (1932) - Lydie Charrington
 Lily Christine (1932) - Mrs. Abbey
 Over the Garden Wall (1934) - Diana
 The Great Defender (1934) - Laura Locke
 Royal Cavalcade (1935) - Undetermined Minor Role (uncredited)
 I Give My Heart (1935) - Marechale
 Cluny Brown (1946) - Lady Alice Carmel
 The Shocking Miss Pilgrim (1947) - (scenes deleted)
 The Homestretch (1947) - Ellamae Scott


Horistomyia

Horistomyia is a genus of crane fly in the family Limoniidae.

Distribution
Australia.

Species
H. leucophaea (Skuse, 1890)
H. occidentalis Alexander, 1929
H. oxycantha Alexander, 1966
H. victoriae Alexander, 1929


Chenaruiyeh, Zarand

Chenaruiyeh (, also Romanized as Chenārū’īyeh and Chenārūyeh; also known as Chanaroo’eyeh Ya’ghoob) is a village in Jorjafak Rural District, in the Central District of Zarand County, Kerman Province, Iran. At the 2006 census, its population was 13, in 5 families.


Michal Šmarda

Michal Šmarda (born 31 January 1971) is a Czech former football midfielder and current coach at FK Baumit Jablonec. He played in the Gambrinus liga, making over 300 appearances for clubs including SK Hradec Králové, FK Viktoria Žižkov and SK Sigma Olomouc. He won the 1998–99 Gambrinus liga with AC Sparta Prague. Šmarda played the final match of his professional career in May 2008 and subsequently moved into coaching.

Coaching career
Šmarda became a coach at Hradec in the Czech 2. Liga in 2008 immediately after ending his playing career. Due to injury problems in the first-team squad, Šmarda played the full 90 minutes in a friendly match for Hradec Králové in February 2012 against FC Astra Ploieşti. In May 2012, Šmarda followed Hradec Králové manager Václav Kotal to FK Baumit Jablonec, becoming assistant manager there.

Honours

Club
Sparta Prague
Gambrinus liga: 1998–99


Mulch-till

In agriculture mulch tillage or mulch-till fall under the umbrella term of conservation tillage in the United States and refer to seeding methods where a hundred percent of the soil surface is disturbed by tillage whereby crop residues are mixed with the soil and a certain amount of residues remain on the soil surface. A great variety of cultivator implements are used to perform mulch-till.

Mulch is material to regulate heat.  This is done by covering it with any material like wood chips, straw, leaves or food waste.