Intended for healthcare professionals

Rapid response to:


Antidepressants and suicide

BMJ 2008; 336 doi: (Published 06 March 2008) Cite this as: BMJ 2008;336:515

Rapid Response:

Antidepressants and suicide: How to avoid the pitfall

The emerging evidence tells us that role of antidepressants in precipitating suicidal behaviour in mood disorders is not a chance association. To elucidate this association, it is important to identify a sub group of patients with mood disorder, who are at risk of exhibiting suicidal behaviour with the use of antidepressants. This is crucial for both safe clinical practice and research.

A depressive episode can be an isolated event or a part of unipolar recurrent depressive disorder or part of Bipolar Affective disorder. The latter manifests in various ways, with depressive episodes or mixed affective episodes at first and mania or hypomania years later, and vice versa. Patients with genetic predisposition to Bipolar disorder, who initially presents with depressive episodes, are at risk of precipitating a mixed depressive or rapid cycling state, if an antidepressant is used on its own. Studies have shown significantly higher rate of suicidal behaviour during such states ( 1). Another group of patients to focus is with Bipolar spectrum disorders, who presents with mixed depressive states, antidepressants induced mixed state or hypomania or depression with background of cyclothymic personality ( 2). Both these groups have higher genetic loading than patients with unipolar depression. This can explain in part, how suicidal behaviour runs in families. For both these groups, the final common pathway leading to suicidal behaviour is precipitation of a mixed depressive state (presence of hypomanic symptoms with in an episode of depression) ( 3). Guilt preoccupation, hopelessness and suicidal thoughts are characteristic thinking patterns (cognitions) in depressed state. Retardation in activities and low energy levels associated with depression, often acts as safety mechanism stopping suicidal action being carried out. In the case of mixed depressive states, hypomanic symptoms like irritability, racing thoughts and psychomotor agitation fuels suicidal thoughts with no safety mechanism holding back. In a recent study, 71% of suicide attempters were found to have current mixed depressive state ( 4). The propensity of antidepressants to induce a mixed depressive state in vulnerable candidates depends on their actions on various neurochemical systems. So serotonergic plus noradrenergic (plus dopaminergic) acting compounds like Venlafaxine, Mirtazapine, TCAs and MAOIs are more “suicide inducing” than SSRIs.( 5). It seems that wider use of SSRIs resulted in more cases of suicidal behaviour reported under its name. However, the prevalence of Bipolar spectrum disorder is lesser than that for depression, in general population. This can explain why this reaction induced by antidepressants is not very common.

An interesting observation in adolescent depression is the higher rate of progression to bipolar disorder in adulthood (20%) (2). Features like earlier onset of depression, hyperphagia, psychotic features, racing thoughts during depression, multiple short episodes of depression indicate underlying vulnerability for Bipolar disorder in adolescents.(2) Use of antidepressants on it’s own in this group of adolescents trigger the reaction reported above. Prevalent use of substances in this age group creates more disinhibiton.

It is therefore important to identify the at risk group of patients, when using antidepressants. Some pointers are mentioned below.(6)

• Previous mixed depressive episodes or bipolar picture.
• Family history of bipolar disorder and suicidal behaviour.
• Current depressive disorder with irritability, racing thoughts, restlessness, psychomotor agitation and distractibility.

So the message to General practitioners, psychiatrists and all who prescribe antidepressants is to look out for the at risk candidates. Closer follow up, shorter course of antidepressants with additional use of mood stabilisers (antiepileptic or atypical antipsychotic) can potentially prevent precipitation of mixed states and the suicidal risk associated, in this group.


1. Rihmer Z. Prediction and prevention of suicide in bipolar disorders. Clinical Neuropsychiatry 2005; 2:48–54.

2. Daniel JS, Blackwood R. Depression in young adults. Advances in Psychiatric Treatment 2004; 10:4-12.

3. RihmerZ. Current Opinion in Psychiatry 2007; 20:17-22.

4. Bala´ zs J, Benazzi F, Rihmer Z, et al. The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention. Journal of Affective Disorder 2006; 91:133–138.

5. Simon GE, Savarino J, Operskalski B, et al. Suicide risk during antidepressant treatment. American Journal of Psychiatry 2006; 163:41–47.

6. Maj M, Pirozzi R, Mangliano L, Batoli L. Agitated Depression in Bipolar 1 Disorder: Prevalence, Phenomenology, and Outcome. American Journal of Psychiatry 2003; 160:2134-2140.

Competing interests: None declared

Competing interests: No competing interests

11 March 2008
Thomas E Elanjithara
Staff Grade Psychiatrist
South London and Maudsley NHS Foundation Trust, 98-102,Northover,BR1 5JX