<unk> s can cause various<unk> verse effects, depending on the individual and the drug in question. 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.<unk> s 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<unk> verse effects, a different type of MAOI has been developed: the reversible inhibitor of monoamine oxidase A (RIMA) class of drugs. Their primary<unk> vantage 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. Tricyclics and SSRI can cause the so-called drug-induced QT prolongation, especially in older<unk> ults; this condition can degenerate into a specific type of abnormal heart rhythm called torsades de points which can potentially lead to sudden cardiac arrest. Some<unk> s are also believed to increase thoughts of suicidal ideation. 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<unk>  use and specific<unk> verse outcomes reflects a causative relationship has been difficult in some cases. In other cases, the attribution of<unk> verse outcomes to<unk>  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<unk> -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 did not reach 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<unk> vises 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<unk>  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<unk>  at birth.<unk> s 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.<unk> -induced mania Another possible problem with<unk> s is the chance of<unk> -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<unk> s. Studies have shown that<unk> -induced mania can occur in 20–40% of people with bipolar disorder. For bipolar depression,<unk> s (most frequently SSRIs) can exacerbate or trigger symptoms of hypomania and mania. Suicide Studies have shown that the use of<unk> s 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<unk> ministration (FDA) to warn of the increased risk of suicidality during<unk>  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<unk>  use and suicidal behavior or thoughts is age-dependent. Compared with placebo, the use of<unk> s is associated with an increase in suicidal behavior or thoughts among those 25 or younger (OR=1.62). A review of RCTs and epidemiological studies by Healy and Whitaker found an increase of suicidal acts by a factor of 2.4. There is no effect or possibly a mild protective effect among those aged 25 to 64 (OR=0.79).<unk>  treatment has a protective effect against suicidality among those aged 65 and over (OR=0.37). Sexual dysfunction 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<unk> s 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. Emotional blunting Certain<unk> s may cause emotional blunting, characterized by reduced intensity of both positive and negative emotions as well as symptoms of apathy, indifference, and amotivation. It may be experienced as either beneficial or detrimental depending on the situation. This side effect has been particularly associated with serotonergic<unk> s like SSRIs and SNRIs, but may be less with atypical<unk> s like bupropion, agomelatine, and vortioxetine. Higher doses of<unk> s seem to be more likely to produce emotional blunting than lower doses. It can be decreased by reducing dosage, discontinuing the medication, or switching to a different<unk>  that may have less propensity for causing this side effect. Changes in weight Changes in appetite or weight are common among<unk> s, 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<unk> s have been shown to contribute to the common side effects of increased appetite and weight gain associated with these classes of medication. Risk of death A 2017 meta-analysis found that<unk> s were associated with significantly increased risk of death (+33%) and new cardiovascular complications (+14%) in the general population. Conversely, risks were not greater in people with existing cardiovascular disease. Discontinuation syndrome<unk>  discontinuation syndrome, also called<unk>  withdrawal syndrome, is a condition that can occur following the interruption, reduction, or discontinuation of<unk>  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<unk>  including selective serotonin re-uptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), and tricyclic<unk> s (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<unk>  fluoxetine which can then be gradually decreased. Approximately 20–50% of people who suddenly stop an<unk>  develop an<unk>  discontinuation syndrome. The condition is generally not
Antidepressant
Antipsychotic
Appetite stimulant
Mood stabilizer
Tetracyclic antidepressant
Tricyclic antidepressant
Atypical antidepressant
Antimanic drugs