<unk><unk> noradrenaline<unk>  inhibitors <unk> s) are a class of antidepressant drugs that treat major depressive disorder (MDD), anxiety disorders, obsessive–compulsive disorder (OCD), social phobia, attention-deficit hyperactivity disorder (ADHD), chronic neuropathic pain, fibromyalgia syndrome (FMS), and menopausal symptoms.<unk> s are monoamine<unk>  inhibitors; specifically, they inhibit the<unk>  of<unk>  and noradrenaline. These neurotransmitters are thought to play an important role in mood regulation.<unk> s can be contrasted with the more widely used selective<unk><unk>  inhibitors (SSRIs), which act upon<unk>  only. The human<unk>  transporter (SERT) and noradrenaline transporter (NAT) are membrane transport proteins that are responsible for the<unk>  of<unk>  and noradrenaline from the synaptic cleft back into the presynaptic nerve terminal. Dual inhibition of<unk>  and noradrenaline<unk>  can offer advantages over other antidepressant drugs by treating a wider range of symptoms. They can be especially useful in concomitant chronic or neuropathic pain.<unk> s, along with SSRIs and noradrenaline<unk>  inhibitors (NRIs), are second-generation antidepressants. Over the past two decades, second-generation antidepressants have simply replaced first-generation antidepressants, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), as the drugs of choice for the treatment of MDD due to their improved tolerability and safety profile. Medications Timeline of approved<unk> s.There are eight FDA approved<unk> s in the United States, with venlafaxine being the first drug to be developed in 1993 and levomilnacipran being the latest drug to be developed in 2013. The drugs vary by their other medical uses, chemical structure, adverse effects, and efficacy. Medication Brand name FDA Indications Approval Year Chemical structure Notes Atomoxetine Strattera * Attention-deficit hyperactivity disorder 2002 center A norepinephrine-predominant<unk>  used in the treatment of ADHD and, off-label, major depression. Was approved by FDA in 2002. Originally considered to be a selective norepinephrine<unk>  inhibitor, but research subsequently revealed that it significantly inhibits the<unk>  of<unk>  at clinical dosages as well. Desvenlafaxine Pristiq Khedezla (ER) * Major depressive disorder 2007 center The active metabolite of venlafaxine. It is believed to work in a similar manner, though some evidence suggests lower response rates compared to venlafaxine and duloxetine. It was introduced by Wyeth in May 2008 and was then the third approved<unk> . Duloxetine Cymbalta Irenka * Major depressive disorder * Fibromyalgia * Generalized anxiety disorder * Diabetic neuropathy * Chronic musculoskeletal pain (e.g., low back pain) * Stress urinary incontinence 2004 center Approved for the treatment of depression and neuropathic pain in August 2004. Duloxetine is contraindicated in patients with heavy alcohol use or chronic liver disease, as duloxetine can increase the levels of certain liver enzymes that can lead to acute hepatitis or other diseases in certain at risk patients. Currently, the risk of liver damage appears to be only for patients already at risk, unlike the antidepressant nefazodone, which, though rare, can spontaneously cause liver failure in healthy patients. Duloxetine is also approved for major depressive disorder (MDD), generalized anxiety disorder (GAD), diabetic neuropathy, chronic musculoskeletal pain, including chronic osteoarthritis pain and chronic low back pain. Duloxetine also undergoes hepatic metabolism and has been shown to cause inhibition of the hepatic cytochrome P450 enzyme CYP 2D6. Caution should be taking Duloxetine with other medications that are metabolized by CYP 2D6 as this may precipitate a potential drug-drug interaction. Levomilnacipran Fetzima * Major depressive disorder 2013 center The levorotating isomer of milnacipran. Under development for the treatment of depression in the United States and Canada, it was approved by the FDA for treatment of MDD in July 2013. Milnacipran IxelSavellaImpulsor * Fibromyalgia * Major depressive disorder 1996 center Shown to be significantly effective in the treatment of depression and fibromyalgia. The Food and Drug Administration (FDA) approved milnacipran for treatment of fibromyalgia in the United States of America in January 2009, however it is currently not approved for depression in that country. Milnacipran has been commercially available in Europe and Asia for several years. It was first introduced in France in 1996. Sibutramine Meridia * Obesity 1997 center An<unk> , which, instead of being developed for the treatment of depression, was widely marketed as an appetite suppressant for weight loss purposes. Sibutramine was the first drug for the treatment of obesity to be approved in 30 years. It has been associated with increased cardiovascular events and strokes and has been withdrawn from the market in several countries and regions including the United States in 2010. Tramadol Ultram * Acute and chronic pain 1977 center A dual weak opioid and<unk> . It was approved by the FDA in 1995, though it has been marketed in Germany since 1977. The drug is used to treat acute and chronic pain. It has shown effectiveness in the treatment of fibromyalgia, though it is not specifically approved for this purpose. The drug is also under investigation as an antidepressant and for the treatment of neuropathic pain. It is related in chemical structure to venlafaxine. Due to being an opioid, there is risk of abuse and addiction, but it does have less abuse potential, respiratory depression, and constipation compared to other opioids (hydrocodone, oxycodone, etc.). Venlafaxine Effexor * Major depressive disorder * Generalized anxiety disorder * Social anxiety disorder * Panic disorder * Chronic pain syndromes *Vasomotor symptoms of menopause (hot flashes) 1994 center The first and most commonly used<unk> . It was introduced by Wyeth in 1994. The<unk>  effects of venlafaxine are dose-dependent. At low doses (150 mg/day), it acts on serotonergic and noradrenergic systems, whereas at high doses (>300 mg/day), it also affects dopaminergic neurotransmission. At small doses, venlafaxine has also been shown to be effective in treating vasomotor symptoms (hot flashes and night sweats) of menopause and may be as effective as hormone replacement therapy (HRT).
Serotonin–norepinephrine reuptake inhibitor
Serotonin–dopamine reuptake inhibitor
Norepinephrine reuptake inhibitor
Glycine reuptake inhibitor
Dopamine reuptake inhibitor
Monoamine reuptake inhibitor
Serotonin–norepinephrine–dopamine reuptake inhibitor
Excitatory amino acid reuptake inhibitor