Antidepressants suicide rates

Khan A, Khan S, Kolts R, Brown WA (2003) Suicide rates in clinical trials of SSRls, other antidepressants, and placebo analysis of FDA reports. Am J Psychiatry 160 790-792 Klein DF (1964) Delineation of two drug-responsive anxiety syndromes. Psychopharma-cologia 5 397-408... 

Anonymous, Antidepressants have been associated with a higher suicide rate. WHO Drug Inf. 7 18-20, 1993. 

The FDA not only limited its suicidality warnings to children, adolescents, and young adults in the new warning but also declared that there was no increase in antidepressant-induced suicidality in adults beyond age 24 and, furthermore, that there was a reduction in risk with antidepressants compared to placebo in adults age 65 and older (GlaxoSmithKline, 2007). The FDA is inviting doctors to believe, based on a small number of elderly patients in short-term clinical trials, that antidepressants might even reduce the suicide rate among older patients. 

Van Pragg, H. (2003). A stubborn behaviour The failure of antidepressants to reduce suicide rates. World Journal of Biological Psychiatry, 4, 184—191. 

Educational policies and commercial marketing of antidepressant drugs have led to an increase in the detection and treatment of depression. Conceivably this may be associated with the fall in suicide rates noted in Finland. However, overdosage of tricyclic antidepressants continues to contribute to deaths from suicide. Whether completely replacing tricyclics with less toxic compounds would lower overall suicide rate remains controversial. 

Interestingly, this decline in antidepressant use appears to have been associated with an increase in suicide rates [48],... 

Toxic Effects of Acute Overdoses Acute poisoning with tricyclic antidepressants or MAO inhibitors is potentially hfe-threatening. Fatalities are much less common since modern antidepressants have widely replaced these drugs however, suicide rates have not declined consistently as clinical usage of modern antidepressants has increased. Deaths have been reported with acute doses of 2 g of imipramine, and severe intoxication can be expected at doses >1 g, or about a week s supply. If a patient is severely depressed, potentially suicidal, impulsive, or has a history of substance abuse, prescribing a relatively safe antidepressant agent with close clinical follow-up is appropriate. If a potentially lethal agent is prescribed, it is best dispensed in small, sublethal quantities, with the risk that sustained adherence to recommended treatment may be compromised. 

Tricyclic antidepressants are cardiotoxic, inducing tachycardias and an increased tendency for ventricular arrhythmias with high doses. This dose dependent cardiotoxicity gives these agents a low therapeutic index. Overdoses are characterized by cardiac conduction disturbances, hyperpyrexia, hypertension, confusion, hallucinations, seizures and coma and there is a high mortality rate in suicide attempts. Depressed patients should therefore not be given more than one week supply of these drugs. 

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. 

One noteworthy naturalistic study (43) compared the incidence of suicidal behavior with the prescribed dose of heterocyclic antidepressant (HCA) and found the rate was 22% for low doses (i.e., less than 75 mg per day) but decreased progressively as the HCA dose was increased (i.e., 11% at 75 to 149 mg per day 1% at 150 to 249 mg per day and 0.5% at 250fall+also mg per day). This finding is even more remarkable considering that the more severely ill patients would be receiving the higher doses. 

Coppen et al. (191) evaluated the status of 104 bipolar or unipolar recurrent patients after 10 years of lithium maintenance to assess mortality rate, in part because of reports indicating unusually high rates, with many deaths attributed to suicide. Compliance was very high, with only 6% discontinuing lithium therapy, and patients also received adjunctive antipsychotic and/or antidepressants when clinically indicated. No patient died of suicide during this period, in contrast to the results in lithium noncompliant patients. The authors concluded that the absence of suicide resulted from the significant reduction in morbidity achieved by the careful administration of lithium. 

Despite the handicap that the studies were largely developed and conducted with the aim of proving the value of industry products, a metaanalysis of the combined data indicated that antidepressants in children and youth increase the suicide attempt rate and that an estimated 1% to 3% of patients would be at risk of antidepressant-induced suicidality (Hammad et al., 2006). On October 15, 2004, the FDA mandated a black-box warning, and in early 2005, it was finalized (FDA, 2005a). According to FDA requirements for describing adverse drug reactions, a risk of 1% or more is considered common. 

The results were striking. When all the pediatric trials were pooled, the rate of definite or possible suicidality among children assigned to receive antidepressants was twice that in the placebo group. (The summary risk ratio was 2.19 95 percent confidence interval.) Although the FDA staff did not provide this information to the committee, according to my own calculations, such a dramatic result could be expected... 

In materials gained through discovery in the Wesbecker case, I found in-house documents from Eli Lilly clearly demonstrating an increased rate of suicide attempts in Prozac patients compared to placebo and to tricyclic antidepressants (Breggin, 1994 available on http //www.breggin. com). This was a shocking discovery as Eli Lilly claimed, and continues to claim, that no such data exist. 

In a prospective cohort study of over 450 patients who had attempted suicide by antidepressant ingestion the risk of seizures after venlafaxine overdose (14%) was significantly greater than that of SSRIs (1.3%) and similar to that seen with dosulepin (11%) (12). Rates of 5HT toxicity did not differ significantly between venlafaxine and SSRIs (29% versus 19%) but were greater than with tricyclic antidepressants (1.2%). Unlike SSRIs, venlafaxine was associated with significant prolongation of the QT interval tricyclic antidepressants had a similar effect. 

A review of the database of the Food and Drug Administration showed 77 suicides among 48 277 patients who had participated in placebo-controlled trials of antidepressants (22). The rate of suicide with SSRIs (0.59% Cl = 0.31, 0.87) was similar to that of other antidepressants (0.76% Cl = 0.49, 1.03) and placebo (0.45% Cl = 0.01, 0.89). While these data are reassuring, patients considered clinically at high risk of suicide were excluded from the trials and the patients received a greater degree of supervision than would occur in routine practice. 

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