<unk>  can increase eye pressure, so those with glaucoma may require more frequent eye checks. A 2017 meta-analysis estimated<unk>  discontinuation rate to 9.4%. Suicide The US Food and Drug Administration (FDA) requires all antidepressants, including<unk> , to carry a black box warning with a generic warning about a possible suicide risk. A 2014 meta analysis of 21 clinical trials of<unk>  for the treatment of depression in adults found that compared to placebo,<unk>  reduced the risk of suicidal thoughts and behavior. A study conducted in Finland followed more than 15,000 patients for 3.4 years.<unk>  increased suicide risk by 60% (statistically significant), as compared to no treatment. At the same time, fluoxetine (Prozac) halved the suicide risk. In another study, the data on more than 200,000 cases were obtained from the UK general practice research database. At baseline, patients prescribed<unk>  had a greater number of risk factors for suicide (such as prior suicide attempts) than patients treated with other anti-depressants. The patients taking<unk>  had significantly higher risk of suicide than the ones on fluoxetine or citalopram (Celexa). After adjusting for known risk factors,<unk>  was associated with an increased risk of suicide relative to fluoxetine and dothiepin that was not statistically significant. A statistically significant greater risk for attempted suicide remained after adjustment, but the authors concluded that it could be due to residual confounding. An analysis of clinical trials by the FDA statisticians showed the incidence of suicidal behaviour among the adults on<unk>  to be not significantly different from fluoxetine or placebo.<unk>  is contraindicated in children, adolescents and young adults. According to the FDA analysis of clinical trials<unk>  caused a statistically significant 5-fold increase in suicidal ideation and behaviour in persons younger than 25. In another analysis,<unk>  was no better than placebo among children (7–11 years old), but improved depression in adolescents (12–17 years old). However, in both groups, hostility and suicidal behaviour increased in comparison to those receiving a placebo. In a study involving antidepressants that had failed to produce results in depressed teenagers, teens whose SSRI treatment had failed who were randomly switched to either another SSRI or to<unk>  showed an increased rate of suicide on<unk> . Among teenagers who were suicidal at the beginning of the study, the rate of suicidal attempts and self-harm was significantly higher, by about 60%, after the switch to<unk>  than after the switch to an SSRI. Discontinuation syndrome People stopping<unk>  commonly experience discontinuation symptoms such as dysphoria, headaches, nausea, irritability, emotional lability, sensation of electric shocks, and sleep disturbance.<unk>  has a higher rate of moderate to severe discontinuation symptoms relative to other antidepressants (similar to the SSRI paroxetine). The higher risk and increased severity of discontinuation syndrome symptoms relative to other antidepressants may be related to the short half-life of<unk>  and its active metabolite. After discontinuing<unk> , the levels of both serotonin and norepinephrine decrease, leading to the hypothesis that the discontinuation symptoms could result from an overly rapid reduction of neurotransmitter levels. Serotonin syndrome The development of a potentially life-threatening serotonin syndrome (also more recently classified as "serotonin toxicity") may occur with<unk>  treatment, particularly with concomitant use of serotonergic drugs, including but not limited to SSRIs and SNRIs, many hallucinogens such as tryptamines and phenethylamines (e.g., LSD/LSA, DMT, MDMA, mescaline), dextromethorphan (DXM), tramadol, tapentadol, pethidine (meperidine) and triptans and with drugs that impair metabolism of serotonin (including MAOIs) . Serotonin syndrome symptoms may include mental status changes (e.g. agitation, hallucinations, coma), autonomic instability (e.g. tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g. hyperreflexia, incoordination) or gastrointestinal symptoms (e.g. nausea, vomiting, diarrhea).<unk> -induced serotonin syndrome has also been reported when<unk>  has been taken in isolation in overdose. An abortive serotonin syndrome state, in which some but not all of the symptoms of the full serotonin syndrome are present, has been reported with<unk>  at mid-range dosages (150 mg per day). A case of a patient with serotonin syndrome induced by low-dose<unk>  (37.5 mg per day) has also been reported. Pregnancy There are few well-controlled studies of<unk>  in pregnant women. A study released in May 2010 by the Canadian Medical Association Journal suggests use of<unk>  doubles the risk of miscarriage. Consequently,<unk>  should only be used during pregnancy if clearly needed. A large case-control study done as part of the National Birth Defects Prevention Study and published in 2012 found a significant association of<unk>  use during pregnancy and several birth defects including anencephaly, cleft palate, septal heart defects and coarctation of the aorta. Prospective studies have not shown any statistically significant congenital malformations. There have, however, been some reports of self-limiting effects on newborn infants. As with other serotonin reuptake inhibitors (SRIs), these effects are generally short-lived, lasting only 3 to 5 days, and rarely resulting in severe complications. Drug interactions<unk>  should be taken with caution when using St John's wort.<unk>  may lower the seizure threshold, and coadministration with other drugs that lower the seizure threshold such as bupropion and tramadol should be done with caution and at low doses. Bipolar disorder<unk>  is neither recommended nor approved for the treatment of major depressive episodes in bipolar disorder, as it can induce mania or mixed episodes.<unk>  appears to be more likely than the SSRIs and bupropion to induce mania and mixed episodes in bipolar patients. Liver injury A rare but serious side effect of<unk>  is liver injury. It reaches male and female patients with a median age of 44y. Cessation of<unk>  is one of the appropriate measure of management. The mechanism of<unk> -related liver injury is unclear but may be related to a CYP2D6 polymorphism. Other In rare cases, drug-induced akathisia can occur after use in some people.<unk>  should be used with caution in hypertensive patients.<unk>  must be discontinued if significant hypertension persists. It can also have undesirable cardiovascular effects.
Venlafaxine
Desvenlafaxine
Nortriptyline
Atomoxetine
Fluoxetine
Amitriptyline
Citalopram
Imipramine