Depression and Suicide Attempts Over Time
Suicide remains impossible to predict, though there have been no shortage of retrospective studies attempting to guide us. Risk factors for suicide attempts include being female (being male confers a greater risk of completed suicide), a history of a prior attempt, younger age, having major depression, psychotic symptoms, borderline personality disorder, alcoholism, and chronic physical illness. Since so many of our patients qualify for so many of these risk factors, it is hard to find much use for them clinically.
A recent study has added something new to our knowledge of suicide risk by following a group of depressed patients over a five-year period to see whether the course of depression predicts the incidence of suicide attempts. In a medium-sized Finish city, 269 depressed patients were enrolled and completed interviews and several psychiatric rating scales. Follow-up interviews occurred at six months, 18 months, and five years. All psychiatric records during follow-up were also available to researchers.
During the five-year follow-up period, 14.5% of participants attempted suicide at least once—53% of participants who attempted suicide did so more than once. Seventy-three percent of attempts occurred during a major depressive episode, 19% during partial remission (one to four depressive symptoms present), and 8% during full remission.
The authors also found that the risk of suicide attempts increased by a factor of 21 during depressed episodes and a factor of four during partial remission, compared to time spent in full remission. While both previous attempts and poor social support also increased risk, the time spent depressed was by far the major risk factor in suicide attempts (Holma KM et al., Am J Psychiatry 2010; 167(7):801–808).
TCPR’s Take: Depressive symptoms were tracked retrospectively, so it is possible that some patients may have incorrectly assumed they were depressed when they made a suicide attempt many months previously. Treatment received was not systematically tracked, so the degree to which various interventions may affect suicide attempts remains unclear. However, the study suggests that achieving at least partial remission greatly reduces suicide attempts; helping to improve social support for our patients may be a particularly efficient way to accomplish this goal, given that social isolation was an independent risk factor.
Fluoxetine May Prevent Relapse After Bipolar II Depressive Episode
The debate over whether patients with bipolar disorder benefit from antidepressants rages on. Another double-blind, placebo-controlled study has recently been added to the mix, this one examining whether fluoxetine (Prozac) monotherapy after a bipolar II depressive episode was superior to lithium monotherapy or placebo in preventing a depressive relapse.
Researchers treated 148 patients aged 18 and older who were currently in a bipolar II depressive episode with Prozac (20 to 80 mg/day) for 12 weeks. Dosage was determined based on response. At the end of this phase, those who had a Hamilton Depression Rating Scale (HAM-D) score of ≤8 (which indicated recovery from the depressive episode) were randomized to one of three conditions for the next 50 weeks. These included 1) Prozac, 10 to 40 mg/day (n=28), 2) lithium, 300 to 1,200 mg/day (to a serum level of 0.5 to 1.5 mmol/liter) (n=26), or 3) placebo (n=27).
The primary outcome measure in this study was time to relapse or recurrence of a major depressive episode. In the Prozac group, the average time to relapse was 250 days. This is significantly longer than the time to relapse for lithium monotherapy (156 days) and the placebo group (187 days).
Researchers also assessed hypomania among all treatment groups. Ten patients in the study had hypomanic episodes: three in the Prozac group, two in the lithium group, and five in the placebo group. The difference in incidence of hypomanic switching among groups was not statistically significant (Amsterdam JD et al., Am J Psychiatry 2010;167(7):792– 800).
TCPR’s Take: This study scores a point for the antidepressant team in the bipolar debate. Patients on Prozac monotherapy not only went longer without a depressive relapse, they also had no greater risk of a hypomanic switch than those on lithium or placebo. One caveat may be that only 54.7% of patients in the original group responded well enough to the 12-week course of Prozac to enter the randomized phase of the trial. This could lead to questions about the severity of illness among this group, and therefore, how representative they are of most patients with bipolar II disorder.
Depakote for Acute Bipolar Depression? Maybe
Treatments for acute bipolar depression are clearly less than ideal. Antidepressants have often shown little benefit for this indication. Quetiapine (Seroquel) has demonstrated efficacy, though its utility for depression in bipolar II is less impressive and its side effect profile is also concerning. Despite often being recommended, lithium has questionable efficacy in acute bipolar depression (Grandjean EM et al., CNS Drugs 2009; 23(3):225–240) and some studies have shown that lamotrigine (Lamictal) has little efficacy in the short-term (Geddes JR, Br J Psychiatry 2009;194 (1):4–9).
A recent meta-analysis examined whether divalproex (Depakote) works for this difficult-to-treat condition. Despite a thorough literature search, only four trials with a total of 142 patients were found. The studies were six to eight weeks in duration. Across three trials, the response rate on Depakote was 39.3% compared to 17.5% in placebo, a significant difference. In four trials, Depakote significantly outperformed placebo in terms of remission rates (40.6% vs. 24.3%). Seven patients would need to be treated with Depakote to generate one additional response or remission that would not have occurred on placebo. Rates of discontinuation due to side effects were not significantly different (4.3% for Depakote and 2.8% for placebo).
TCPR’s Take: The data are quite limited, but they suggest that Depakote may be modestly effective for bipolar depression.