Suicide Attempts in Patients With Bipolar I Disorder During Acute and Maintenance Phases of Intensive Treatment With Pharmacotherapy and Adjunctive Psychotherapy

Ninety-eight women and 77 men participated in the study. The mean age was 35.1 years (SD=10.5) and the mean educational level 14.8 years (SD=1.9). Ninety percent (N=158) were European American, and 42.3% (N=74) were single, 36.0% (N=63) were married, 20.6% (N=36) were divorced or separated, and 1.1% (N=2) were widowed.

During the acute treatment phase, 92 patients (52.6%) were predominantly treated for depression, 40 (22.9%) for mania, and 43 (24.6%) for mixed or cycling episodes.

The clinical characteristics of the study subjects are reported in Table 1. Of the 175 patients, 166 (94.9%) were treated with lithium during the majority of the protocol. The mean plasma lithium level in these subjects was 0.83 meq/liter (SD=0.22, range=0.32–1.21).

We computed rates of prior suicide attempts beginning from the estimated date of onset of illness to the entry into acute treatment phase. The period considered for the calculation of the months at risk under treatment was between August 15, 1991 and December 5, 2000.

Seventy-two attempts were identified to have occurred before the patients entered the protocol. These 72 attempts occurred in 50 subjects, none of whom attempted suicide during the protocol. Eleven subjects reported making multiple attempts: six subjects reported two attempts, two reported three attempts, and three reported five attempts. Of these 72 attempts, five occurred in individuals who were taking lithium, seven in individuals taking antidepressants, one in an individual taking other psychotropic medications, and 44 in individuals who were not taking any medications for their mood disorder at the time of the attempt. Three attempts occurred in individuals who were receiving psychosocial treatment alone. For the remaining 12 attempts, Life-Chart data on the subject’s treatment were missing. Overall, four attempts occurred in subjects who were receiving both psychosocial treatment and medication.

Five suicide attempts occurred during the protocol, four during the acute treatment phase and one during the maintenance phase. At the time of the attempts, three of the patients were taking lithium, one had stopped taking lithium 2 days before the attempt, and one was taking divalproex. In the week before the attempt, three subjects were mildly to moderately depressed (Hamilton depression scale score between 14 and 27), one had low depression and mania ratings (Hamilton depression scale score=6, Bech-Rafaelsen Mania Scale score=0), and one patient had mixed symptoms, evidenced by relatively severe depression and mania ratings (on the day before the suicide attempt: Hamilton depression scale score=22, Bech-Rafaelsen Mania Scale score=21). At the time of the suicide attempt, four patients were receiving intensive clinical management in the acute phase and one was receiving interpersonal and social rhythm therapy in the maintenance phase.

Forty-seven subjects failed to complete the acute phase, and 20 failed to complete the maintenance phase. The reasons for study termination were termination against medical advice (N=35), failure to stabilize and/or intolerable side effects (N=16), termination with medical advice (N=4), and other reasons (e.g., moved out of town) (N=12).

In the entire subject group, a base rate of 1.05 attempts per 100 patient-months was computed for the period before study entry. During the acute phase, the rate of suicide attempts per 100 patient-months was 0.31, a threefold reduction in this short period relative to the period before entering the study. During the maintenance phase, the rate of attempts per 100 patient-months was 0.06 (a 17.5-fold reduction) (Figure 1). Using Poisson loglinear regression to model the relationship between the number of suicide attempts and the protocol stage (pretreatment, acute, maintenance), we found that these reductions were significant both in the acute (χ²=5.70, df=1, p<0.02) and in the maintenance phase (χ²=8.28, df=1, p=0.004), compared to the pretreatment phase. When we compared the rate of suicide attempts during the maintenance phase with the rate during the acute phase, the difference was not significant at the p<0.05 level. The mode-specific rates were 0.26 for patients receiving intensive clinical management and 0.07 for patients receiving interpersonal and social rhythm therapy, again with no significant difference. Overall, the rate was 0.17 during the protocol, corresponding to a six-fold reduction.

The present attempt to examine the impact of psychosocial treatment and a maximally supportive clinic environment on the rate of suicide attempts in individuals with bipolar disorder is limited in several ways. We acknowledge that the study inclusion and exclusion criteria may have led to a selection bias favoring patients with less complicated forms of bipolar disorder. However, this limitation is somewhat mitigated by the fact that we examined each patient as his or her own comparison subject. A second limitation, while a very satisfying outcome from the standpoint of clinical care, is the low rate of suicide attempts during the protocol itself, which leads to low power for statistical analysis. This limitation is common to many studies, leading to a virtual absence of data on nonfatal suicidal behaviors, as claimed in a recent Cochrane review (19) on lithium effect for maintenance treatment of mood disorder. This lack of data made the authors conclude that “it is impossible to draw meaningful conclusions about the place of lithium therapy in suicide prevention” (19). Finally, it is possible that the Life-Chart method, which depended partially on subjects’ recall, could have underestimated the actual number of suicide attempts before study entry, failed to represent the lethality of attempts accurately, or in other ways biased these analyses. In point of fact, the majority of the attempts included in our analyses were well documented in medical charts, thus somewhat reducing the likelihood that they were improperly characterized.

We found a consistent reduction in suicide attempt risk  associated with a combination of pharmacotherapy (mostly lithium) and either a highly structured psychosocial treatment designed specifically for individuals with bipolar I disorder or a more general supportive intervention offered in the context of a research clinic environment geared toward optimal care of patients with this condition. This reduction is more pronounced during the maintenance phase than during the acute phase. In their review of the results of 33 studies, yielding 13-fold lower rates of suicide and reported attempts during long-term lithium treatment than without it or after its discontinuation, Baldessarini et al. (4) suggested that the protection against suicide offered by lithium is substantial but incomplete and that the evaluation of alternative treatments is required. Our results provide preliminary evidence that intensive clinical management or psychotherapy add to the effect of lithium or other appropriate pharmacotherapy. Our study setting is unique in that patients were seen at least monthly, monitored for treatment adherence, traced if they miss appointments, received medications at no cost, and had access to a 24-hour on-call service operated by the clinic staff. Thus, the study allowed examination of the benefit of treatments in optimal conditions. Although the overall suicide risk during the protocol was low, it is noteworthy that four of the five suicide attempts observed occurred among subjects who were being followed with clinical management as opposed to interpersonal and social rhythm therapy, suggesting that disorder-specific psychotherapy may have effects on suicidal behavior over and above the protective effect of a highly supportive clinical milieu. It is important to underscore the potential role for suicide prevention when clinical trials are conducted in a structured clinical setting. Such clinical settings often provide a 24-hour emergency on-call system for patients and an ongoing “safety net” through attention of multiple staff members to each patient’s clinical state. Patients educated about early warning signs of an impending relapse can best take advantage of this clinical milieu. In short, we believe that study settings such as the one in which this clinical trial was carried out provide the first line of defense and that disorder-specific psychotherapy coupled with adequate pharmacological interventions provide the second line of defense. The ongoing NIMH-supported Systematic Treatment Enhancement Program in Bipolar Disorder (G. Sachs, personal communication, 2001) should provide additional information on this point in a study with adequate power to test this important question.

Even these preliminary data provide some evidence that it is possible to decrease the high risk of suicidal behavior associated with bipolar disorder through vigorous treatment. Should similar results occur in the Systematic Treatment Enhancement Program in Bipolar Disorder, the combined findings will provide a powerful argument for increased intensity of care for patients with bipolar I disorder.

Received Aug. 8, 2001; revision received Feb. 2, 2002; accepted March 5, 2002. From the Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh. Address reprint requests to Dr. Frank, Western Psychiatric Institute and Clinic, 3811 O’Hara St., Pittsburgh, PA 15213; [email protected] (e-mail). Supported by NIMH grants MH-29618 (Dr. Frank) and MH-30915 (Dr. Kupfer) and an unrestricted grant from Merck Laboratories (Dr. Frank). The authors thank Patty Houck for advice on SAS procedures for weighted Poisson regression.