Clinical variables related to antidepressant-induced mania in bipolar disorder

Abstract

Background

The development of mania or hypomania during antidepressant treatment is a serious complication of the clinical management of bipolar disorder (BP). The primary aim of this study was to evaluate the clinical variables related to antidepressant-induced mania or hypomania (AIM) in patients with BP.

Methods

DSM-IV BP-I or BP-II patients who had had at least one depressive episode treated with antidepressants were considered. Patients were subdivided into two groups according to the presence (n = 30) or absence (n = 106) of manic or hypomanic episodes occurring during antidepressant treatment. Possible predictive clinical variables of AIM were considered: gender, diagnostic subtype, age at onset, duration of illness, duration of untreated illness, type of antidepressant administered, number of previous spontaneous hypomanic or manic episodes, number of previous depressive episodes, presence of lifetime suicide attempts, presence of mood stabilizer treatments, presence of psychotic symptoms during spontaneous episodes, family history for psychiatric disorders in first degree relatives. Data were compared between the two groups, with (AIM+) and without (AIM−) antidepressant-induced mania, using Student's t tests and chi-square tests.

Results

The lack of mood stabilizer treatments during antidepressant therapy (chi-square = 37.602, df = 1, p < 0.001) and the exposure to tricyclic antidepressants (chi-square = 4.901, df = 1, p < 0.05) resulted significantly associated to the development of AIM.

Limitations

This study was not done under controlled conditions and the relatively small sample studied warrants further replications.

Conclusions

These results point out the risk of mania induction associated to the use of tricyclic antidepressants in BP patients, mainly in absence of adequate mood stabilizers.

Introduction

The induction of mania during antidepressant treatment of bipolar depression is not a rare phenomenon, occurring in up to 70% of bipolar disorder (BP) patients (Angst, 1985, Altshuler et al., 1995, Mundo et al., 2001, Goldberg and Truman, 2003).

Some studies have focused on the possible clinical predictors of this phenomenon.

Whether the type of antidepressant treatment can influence the risk of mood switches remains controversial. According to Solomon et al. (1990), a manic switch during antidepressant treatment may occur in 20% of the BP inpatient admissions regardless of treatment status (tricyclic antidepressants —TCAs, monoamine oxidase inhibitors —MAOIs or electroconvulsive therapy —ECT). However, some reports showed that the rate of induction of mania is higher in BP patients treated with TCAs and MAOIs than in BP patients treated with selective serotonin reuptake inhibitors (SSRIs) (Peet, 1994, Boerlin et al., 1998).

A higher number of previous manic or hypomanic episodes appeared to be a clinical variable affecting the risk for developing mania during antidepressant treatment in some studies (Angst, 1985, Boerlin et al., 1998) but not in all (Altshuler et al., 1995).

There are data on a greater risk of AIM in BP-I rather than in BP-II patients (Himmelhoch et al., 1991). However, this conclusion has not been confirmed in more recent studies (Henry et al., 2001). Other data show that BP patients with hyperthymic temperament have a greater risk to develop mania during the antidepressant treatment (Henry et al., 1999, Henry et al., 2001), and that AIM is more frequent in subjects with a positive family history for mania or hypomania (Howland, 1996).

The role of mood stabilizers in preventing AIM during the treatment of bipolar depression has been also considered with mixed results (Henry et al., 2001, Mundo et al., 2001).

The primary aim of this study was to evaluate the clinical variables related to AIM in patients with BP treated with oral antidepressants.