May 21, 2010

Clarification on antidepressants and potential adverse effects

The College of Psychiatry of Ireland issued the following press statement last week, entitled ‘Anti-depressant Medication – Clarification’, which clarified its position on antidepressants and violent acts

Untreated depression can have a fatal outcome. Those experiencing moderate to severe depression frequently describe having thoughts of suicide. Suicidality (a spectrum of thinking and behaviour, from the person thinking of no longer being alive or a having a passive death wish to suicidal thoughts and/or suicidal acts) is one of the core symptoms of a depressive episode according to the two universally recognised psychiatric diagnostic systems.

The lifetime risk of completed suicide approximates 6 per cent in unipolar or bipolar depression and may be closer to 15 per cent in severe depression. Antidepressants are effective in the treatment of depression and thus lead to a reduction in suicidal thoughts. The effective treatment of depression is an important means of reducing suicide rates.

Indications for anti-depressant use
Antidepressant medications are approved by the Irish Medicines Board (IMB). The indications for which antidepressants are licensed in Ireland include major depressive episodes, obsessive-compulsive disorder, posttraumatic stress disorder, bulimia nervosa and anxiety disorders. About 3 per cent of Irish adults are current users of antidepressants.

Adverse effects
People taking antidepressant drugs may experience adverse effects. In the past month, there has been considerable discussion in Ireland of suicidality and homicidality as potential adverse effects of antidepressant medications, and selective serotonin reuptake inhibitor (SSRI) antidepressants in particular. Much of this discussion has been speculative.

Clearly, suicide and homicide are events of the utmost gravity and any possible role of any treatment in precipitating such tragedies warrants the most thorough investigation. However, discussion of the risks involved must be based on evidence rather than conjecture or unfounded personal opinion.

In 2006, following formal evaluation at European Union level, the Irish Medicines Board, in conjunction with its EU counterparts, updated the production information that comes with antidepressants to warn of a possible increase in suicidality during treatment, especially among children and young adults. A review was also conducted in the US, by the Food and Drug Administration (FDA), with similar advice issued.

Of note, studies involving older patients have shown a reduction in suicidality. A very large American study from 2006, coming after the FDA’s new recommendations, found that the risk of attempted suicide declined progressively after antidepressant initiation, from a peak in the month before treatment; there was no change during early treatment in the rate of completed suicide.

At an individual level, treatment usually commences at a point when the patient’s depression is worsening. As the therapeutic effect of antidepressants can be delayed for several weeks, there can be a period, early in treatment, when the illness is unresponsive (and possibly progressing) before the restorative effect of the treatment emerges. This leads to a period of risk following commencement which requires additional non-pharmacological support.

Anecdotal cases of suicide sometimes mistakenly attribute these tragic events to the treatment rather than the illness itself. Also, people who are beginning to respond to antidepressant treatment may be more able, as energy and motivation returns, to act on suicidal thoughts that are inherent to their condition. That the early recovery period is potentially a period of increased risk for suicidality is something of which all doctors should be aware.

The College of Psychiatry of Ireland, in unison with the IMB’s advice, recommends close monitoring of all individuals commenced on antidepressant therapy.

There is no evidence of a link between antidepressant use and homicide. Commentators who assert that there is such a link rely largely on a small number of case reports of individuals who were homicidal after commencing antidepressants. However, case reports cannot demonstrate a causal link.

They cannot allow for the many factors that determine whether or not a person chooses to commit a violent crime. It is a fundamental error of thinking to argue that one event was caused by another because it occurred shortly afterwards.

Homicide by people who have recently started anti-depressants is incredibly rare, but it occurs. It is not reasonable to expect that no person who had recently commenced antidepressants would ever commit violent crime.

Antidepressants do not cause violence. Neither are they, nor can they be expected to be, an inoculation against violence. The alleged link between antidepressants and violence is partly based on observation of an ‘activation syndrome’, which includes agitation, irritability, impulsivity and akathisia.

Akathisia is an unpleasant sense of inner restlessness that is often medication-related. It is an uncommon side effect of antidepressants, cited by some authors as a particular risk factor for violence. The leap from observing restlessness in an individual to imputing homicidal risk is a large one. No study has demonstrated a link between ‘activation syndrome’ and homicide or homicidality.

Evidence at recent inquest
Evidence was given in a recent inquest at the Wicklow Coroner’s Court that the self-inflicted death of a person (and by inference, the killing of another person) was most likely the direct result of SSRI antidepressant use – specifically, citalopram. The College of Psychiatry of Ireland is conscious that the events leading to these deaths are not completely understood nor is the mental state of the individual at the time.
We address the inquest here simply to respond to the sworn expert evidence, which was, in our view, speculative. It was claimed that an individual may have acted as he did because he was in a supposed ‘delirium’, brought about by high blood levels of citalopram, on the night in question.

A delirium is a syndrome characterised by fluctuating consciousness, disorientation to time, place, or person, and profound impairment of memory and attention. A person experiencing a delirium is incapable of deliberate and planned activity.

This description is not consistent with the sworn evidence of the individual’s behaviour of that night. This expert’s justification of his delirium hypothesis on the grounds that the attack was ‘quite frenzied’ is a non sequitur. There are no grounds to claim that a ‘frenzied’ attack suggests delirium.

It was further suggested by this expert witness that if not a delirium, the explanation could have been a ‘mental automatism’ caused by SSRI intoxication. Automatism refers to motor (not mental) activity, which, while appearing to the observer to be similar to purposeful behaviour, is performed in a semiconscious state without awareness of one’s surroundings.

A sequence of acts requiring awareness of one’s environment and sequential planning is not consistent with automatism. There is no evidence that automatism is related to SSRI antidepressant drugs nor is there any credible evidence that automatism was involved in the events that culminated in two deaths and two other people being non-fatally stabbed in Bray in August 2009.

Concerns regarding stigma
The College of Psychiatry of Ireland is concerned that a mooted link between antidepressants and violence, which does not have a basis in scientific evidence, risks perpetuating a false and stigmatising stereotype that people living with mental illness are violent.

We would direct those interested in the matter to a seminal study recently published in the world’s most prestigious psychiatry journal. The take-home message of this prospective study of almost 35,000 people was that mental illness alone did not predict future violent behaviour. This is one of the most important findings in mental health research.

In light of this and other findings, the College urges interested parties to avoid linking acts of violence to the symptoms or treatment of mental disorder without considering the evidence and the facts of each case.