Suicidal Thoughts and Behavior With Antidepressant Treatment

Abstract

Context The US Food and Drug Administration issued a black box warning for antidepressants and suicidal thoughts and behavior in children and young adults. Objective To determine the short-term safety of anti-depressants by standard assessments of suicidal thoughts and behavior in youth, adult, and geriatric populations and the mediating effect of changes in depressive symptoms. Data Sources All intent-to-treat person-level longitudinal data of major depressive disorder from 12 adult, 4 geriatric, and 4 youth randomized controlled trials of fluoxetine hydrochloride and 21 adult trials of venlafaxine hydrochloride. Study Selection All sponsor-conducted randomized controlled trials of fluoxetine and venlafaxine. Data Extraction The suicide items from the Children’s Depression Rating Scale–Revised and the Hamilton Depression Rating Scale as well as adverse event reports of suicide attempts and suicide during active treatment were analyzed in 9185 patients (fluoxetine: 2635 adults, 960 geriatric patients, 708 youths; venlafaxine: 2421 adults with immediate-release venlafaxine and 2461 adults with extended-release venlafaxine) for a total of 53 260 person-week observations. Data Synthesis Suicidal thoughts and behavior decreased over time for adult and geriatric patients randomized to fluoxetine or venlafaxine compared with placebo, but no differences were found for youths. In adults, reduction in suicide ideation and attempts occurred through a reduction in depressive symptoms. In all age groups, severity of depression improved with medication and was significantly related to suicide ideation or behavior. Conclusions Fluoxetine and venlafaxine decreased suicidal thoughts and behavior for adult and geriatric patients. This protective effect is mediated by decreases in depressive symptoms with treatment. For youths, no significant effects of treatment on suicidal thoughts and behavior were found, although depression responded to treatment. No evidence of increased suicide risk was observed in youths receiving active medication. To our knowledge, this is the first research synthesis of suicidal thoughts and behavior in depressed patients treated with antidepressants that examined the mediating role of depressive symptoms using complete longitudinal person-level data from a large set of published and unpublished studies.

The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439Hisknockin mouse

“…It is thus tempting to hypothesize that 5-HT deficiency is a significant causal factor in a specific subset of depression patients. This view would be consistent with the general clinical finding in double-blind SSRI antidepressant trials: at best, SSRIs produce a 10-20% greater response rate in patients receiving the drug versus those treated with placebo [94,95]. In fact, SSRIs fail to show superior antidepressant effect compared with placebo in 40 per cent of clinical trials [9,11].…”

The drugs don’t work? antidepressants and the current and future pharmacological management of depression

“…A more recent meta-analysis [Gibbons et al 2012] re-analysing these data sets failed to show an increase in suicide risk in young people on either venlafaxine or fluoxetine, although they showed therapeutic benefit in the treatment of their depression; in working age and older adults there was a decrease in suicidal thoughts and behaviour that was mediated by treatment of depression.…”

Suicides and Suicide Attempts during Long-Term Treatment with Antidepressants: A Meta-Analysis of 29 Placebo-Controlled Studies Including 6,934 Patients with Major Depressive Disorder

“…Nevertheless, randomized trials of antidepressant pharmacotherapy lend themselves to analyses with regard to suicidality. For example, Gibbons et al [17] report that fluoxetine and venlafaxine reduce suicidality, as measured primarily by using suicidality items on rating scales (HMA-D, CDRS-R). This is an indirect measurement considering that suicidal thoughts constitute the most part of what is considered suicidality in this analysis and that they are only weak predictors of completed suicides.…”