Fluoxetine and suicidality

Koizumi, J. (1991). Fluoxetine and suicidal ideation. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 695. 

Beasley CM Jr, Domseif BE, Bosomworth JC, Sayler ME, Rampey AH Jr, Heiligenstein JH, Thompson VL, Murphy DJ, Masica DN. Fluoxetine and suicide a metaanalysis of controlled trials of treatment for depression. BMJ 1991 303(6804) 685-92. 

Beasley, C. M., and B. E. Domseif. 1991. Fluoxetine and suicide A meta-analysis of controlled trials of treatment of depression. British Medical Journal 303 685-92. 

Adverse reactions include nausea, nervousness, headache, insomnia, anxiety. Sexual dysfunction with loss of libido is a common complaint. Insomnia can be a problem. Urticaria and rashes have been described. Venlafaxine may significantly increase the risk of suicide and is therefore not recommended as a first line treatment of depression. The view that also fluoxetine and other SSRIs can lead to suicide is under debate for quite some time now. In most countries SSRIs are not approved for use in pediatric populations. In the UK and in the USA only fluoxetine can be prescribed for children. 

The side effects of antidepressants, sometimes very unpleasant, olten lead patients to interrupt their treatment or to reduce the drug dose, which involves a great risk in view of the high relapse rate and danger of suicide in depression. The newer antidepressants, such as trazodone, fluoxetine and other SSRIs and moclobemide, are characterized by better tolerability and lower toxicity and are therefore preferred in the treatment of outpatients and elderly patients (Rudorfer and Potter, 1989). A detailed list of general and specific common side effects associated with the newer generation of antidepressants is seen in Table 1.7. 

Leon AC, Keller MB, Warshaw MG, et al. Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects. Am J Psychiatry 1999 156 195-201. 

Wirshing W, Van Putten T, Rosenberg J, et al. Fluoxetine, akathisia and suicidality is there a causal connection [Letter] Arch Gen Psychiatry 1992 49 580-581. 

Muijen et al. (1988) conducted a 6-week double-blind study comparing fluoxetine, mianserin, and placebo with 26, 27, and 28 starters, respectively, and 14, 14, and 16 finishers, respectively. Two of the fluoxetine patients took an overdose within two weeks of starting the study, and in both cases this was related to a deteriorating clinical state that necessitated hospitalization (p. 386). None of the patients in the other drug group or the placebo group suffered from this decline and suicidality. 

Bost and Kemp (1992) reviewed a series of coroner s reports in Dallas, Texas, involving 15 suicides associated with fluoxetine treatment. The study covered a 9-month period. While they appreciated that their data were impressionistic, they warned that the proportion of patients taking fluoxetine and committing suicide was high enough to be of concern to health care providers. 

Wirshing et al. (1992) reported on five cases of a fluoxetine-induced syndrome consisting of akathisia and suicidality. In all five cases, the akathisia and the suicidality remitted when the drug was stopped or reduced in dosage. In one case, a rechallenge with an increased dose of fluoxetine again produced the syndrome. They concluded, Our cases appear to confirm that certain subjects experience akathisia while taking fluoxetine and... 

Creaney et al. (1991) described two patients who became suicidal on SSRIs. One patient developed dysphoria and manic symptoms on fluoxetine and then developed a similar syndrome, this time with suicidal feelings, on fluvoxamine. Another patient became intensely and violently suicidal 16 days after starting fluoxetine. 

Fisher et al. (1993) conducted a phone survey of pharmacy patients taking various antidepressants and compared fluoxetine to trazodone. They concluded that fluoxetine caused a higher incidence of psychologic/ psychiatric adverse clinical events, including delusions and hallucinations, aggression, and suicidal ideation (p. 235, emphasis added). In a followup study, Fisher et al. (1995) found that many of the same side effects reported in regard to Prozac were also reported for Zoloft. Both drugs... 

Bost, R. O., 6c Kemp, P. M. (1992, March/April). A possible association between fluoxetine use and suicide. Journal of Analytical Toxicology, 16, 142—145. 

Wirshing, W., Van Putten, T., Rosenberg, J., Marder, S., Ames, D., Hicks-Gray, T. (1992). Fluoxetine, akathisia, and suicidality Is there a connection Archives of General Psychiatry, 49, 580-581. 

Five patients taking fluoxetine developed akathisia, perhaps due to enhanced serotonergic inhibition of dopamine neurons (9). A causal link between fluoxetine-induced akathisia and suicidal behavior has been suggested (SEDA-17, 19) (SEDA-18, 19), and akathisia has also been associated with indifference (SEDA-18, 19). 

In an analysis of data from the National Institute of Mental Health Collaborative Depression Study in 643 patients with affective disorders who were followed up after fluoxetine was approved by the FDA in December 1987 for the treatment of depression, nearly 30% (n = 185) took fluoxetine at some point (18). There was an increased rate of suicide attempts before fluoxetine treatment in those who subsequently took fluoxetine. Relative to no treatment, fluoxetine and other antidepressants were associated with non-significant reductions in the likelihood of suicide attempts or completions. Severity of psychopathology was strongly associated with increased risk, and each suicide attempt after admission to the study was associated with a marginally significant increase in the risk of suicidal behavior. The authors concluded that the results did not support the speculation that fluoxetine increases the risk of suicide. 

Bupropion, mirtazapine, reboxetine, or atomoxetine (add with caution and at lower doses since fluoxetine could theoretically raise atomoxetine levels) use combinations of antidepressants with caution as this may activate bipolar disorder and suicidal ideation... 

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have been associated with increasing suicidal ideation in some populations of patients. Recent studies have led the British Department of Health to warn physicians against using paroxetine off label. Fluoxetine was specifically exempted from this recommendation. Long-term studies of patients with depression who were treated with fluoxetine have shown it to be fairly well tolerated. Primary adverse effects include nausea (23%), headache (21%), and insomnia (20%). 

Suicidality in children and adolescents Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of olanzapine/fluoxetine or any other antidepressant in a child or adolescent must balance this risk with clinical need. 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

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