Reducing suicide risk in psychiatric disorders
Antidepressants show little protective effect in major depression, but more promising evidence is emerging for treating patients with bipolar or psychotic disorders.
Anticonvulsants. Evidence regarding the effects of other mood stabilizers on suicide risk in bipolar disorder remains limited:
- In a European collaborative study, several hundred patients with bipolar or schizoaffective disorder were randomly assigned to receive lithium or carbamazepine for nearly 2 years. Rates of suicidal acts were 2.5%/year with the anticonvulsant, but there were no suicides or attempts in patients receiving lithium.17 Direct comparisons are rare, but this difference was both striking and statistically significant.
- Computerized records of approximately 20,000 patients diagnosed with bipolar disorder at two large American HMOs were analyzed to compare suicidal behaviors associated with specific treatments. Lithium yielded 2.7-fold greater protection against suicidal behavior (mainly attempts because suicides were rare) compared with anticonvulsants (mainly divalproex).18
Treatment recommendation. These observations support lithium’s value in long-term maintenance of patients with bipolar disorder. Lithium’s apparent reduction of suicide risk is striking and may be superior to that of other mood-stabilizers. Alternate treatments and lithium’s potential value for reducing suicide risk in patients with unipolar depression require further study.
It is important to emphasize that lithium can be toxic or even fatal in acute overdose. This risk is integral to the equation when you assess risks and benefits for individual patients.
MAJOR DEPRESSION AND ANTIDEPRESSANTS
Major depression and depressive components of other disorders are major risk factors for suicide.1,2,6 Depression continues to be surprisingly underrecognized and undertreated, even though relatively safe and tolerable antidepressants are readily available.1,6,19,20 Patients with recurrent unipolar major depression often remain inconsistently or inadequately treated, even after they attempt suicide.19
Recent reviews of suicide risk during research on antidepressant treatment in major depression suggest that:
- antidepressants of various kinds may tend to reduce the risk of suicidal behavior, but any such effect is small and statistically nonsignificant (Baldessarini et al, 2003, unpublished)
- tricyclic antidepressants may yield lower rates of suicidal behavior than selective serotonin reuptake inhibitors (SSRIs). Similarly, however, such trends reflect highly variable research methods and inconsistent findings and do not hold up to quantitative analysis (Baldessarini et al, 2003, unpublished).
The suicidal events encountered during research mainly involve attempts because suicides are rare, particularly in relatively brief treatment trials that exclude acutely suicidal subjects. Analyses are further complicated by trends toward paradoxically lower suicidal risks among depressed patients randomized to a placebo in controlled antidepressant trials. This paradox is paralleled by often earlier removal of patients treated with a placebo than with an active antidepressant, perhaps in association with emerging suicidality.21
Table 3
Preventing suicide: How effective are specific treatments?
| Treatments compared | Disorder treated | Benefit/risk ratio |
|---|---|---|
| Mood stabilizers | ||
| Lithium vs. none or placebo* | Bipolar disorder | |
| Suicides | 8.8 (4.1 to 19.1)a | |
| Attempts | 9.9 (5.0 to 14.8)b | |
| Lithium vs. carbamazepine* | Bipolar disorder | ≥2.5c |
| Lithium vs. divalproex* | Bipolar disorder | 2.7 (1.2 to 6.2)d |
| Antidepressants | ||
| Antidepressants (any) vs. placebo/none | Major depressive disorder | 1.1 (0.7 to 1.6)e |
| Tricyclics vs. SSRIs | Major depressive disorder | 1.2 (0.7 to 2.1)e |
| Antipsychotics | ||
| Clozapine vs. any antipsychotic* | Schizophrenia | |
| Suicides + attempts | 3.3 (1.7 to 6.3)f | |
| Attempts | 2.9 (1.5 to 5.7)f | |
| Clozapine vs. olanzapine* | Schizophrenia | |
| Suicides + attempts | 1.3 (1.0 to 1.7)g | |
| a. Tondo et al, 200111 | ||
| b. Baldessarini et al, 20035 | ||
| c. Thies-Flechtner et al, 199517 | ||
| d. Goodwin et al, 200218 | ||
| e. Baldessarini et al, 20035 | ||
| f. Baldessarini & Hennen, 200322 | ||
| g. Meltzer et al, 200324 | ||
| * First agent is statistically more effective, based on benefit/risk ratio (95% CI). | ||
These trends toward lower suicide risk among patients receiving a placebo are somewhat reassuring, given concern that placebo randomization for scientific purposes may endanger study subjects. However, these artifacts confound interpretation of results and make it difficult to measure the effects of antidepressant treatment.
Treatment recommendation. Clinical prudence requires us to treat potentially lethal major depressive illness aggressively, even though one cannot state with confidence that any antidepressant class lowers suicide risk or that one class is significantly more effective than others (Table 3).
SCHIZOPHRENIA AND ANTIPSYCHOTICS
For schizophrenia and other primary psychotic disorders, little research exists to indicate that atypical antipsychotics reduce suicide risk. Evidence is emerging, however, that clozapine may offer this benefit,22 in addition to its well-substantiated clinical superiority in treatment-resistant psychotic illness.23
Pooled evidence from controlled trials comparing clozapine with other antipsychotics indicates a 2-fold lower risk of mortality from all causes.23 This finding was highly suggestive but not statistically significant, and the specific contribution of suicide to this risk is unknown.23 Our recent meta-analysis of the few available studies found that clozapine was associated with a statistically significant, 3.3-fold lower overall suicidal risk compared with other antipsychotic treatments.22
A well-designed, 2-year study randomly assigned 980 patients with schizophrenia or schizoaffective disorder who were at high risk for suicide to clozapine (mean 274 mg/d) or olanzapine (mean 16.6 mg/d). Clozapine showed moderately greater benefit in reducing suicide attempts and need for urgent intervention for perceived emerging suicide risk, although it did not lower suicide risk per se.24 Another study associated olanzapine with a 2.3-fold lower risk of suicidal behavior, compared with haloperidol.25
