Antidepressant-Induced Mood Conversions in Bipolar Disorder: A Retrospective Study of Tricyclic versus Non-Tricyclic Antidepressant Drugs

Abstract

Objectives: The aim of this retrospective study was an analysis of antidepressant-induced mood conversions to mania/hypomania occurring in bipolar inpatients treated with antidepressants in the Affective Disorder Unit of the Institute of Psychiatry and Neurology, Warsaw, in the years 1972–1996. Methods: The data for analysis were obtained retrospectively from clinical records. In a subgroup of patients prone to mood conversions, a comparison was done of depressive episodes treated with antidepressants with and without a switch to mania/hypomania as well as the frequency of mood conversions induced by particular antidepressant drugs, especially tricyclic (TCA) versus non-TCA drugs. Results: Among 333 bipolar patients hospitalized in this period, mood conversions were observed in 118 subjects, significantly more frequently in female (44%) than in male patients (25%), and in patients with depressive episode at the onset of illness (80 vs. 40%). Among mood converters, it was found that the depressive episodes with a switch to mania were less severe, shorter, and with shorter duration of antidepressant treatment. The risk of switching was higher during treatment with TCA than with non-TCA drugs (36 vs. 17%), the highest with amitriptyline (42% of treated episodes), imipramine (40%) and clomipramine (35%). Conclusions: Our results suggest that bipolar patients prone to mood conversion constitute one third of the inpatient population with this illness. The switch from depression to mania occurred significantly more frequently during treatment with TCA than with non-TCA drugs. It is hypothesized that anticholinergic activity may contribute to the higher frequency of TCA-induced mood conversions.

Animal models of bipolar mania: The past, present and future

“…Resident mice treated with lithium for 4 weeks before the test exhibited a significant reduction in the number of attacks against intruder mice compared with controls but did not show any difference in non-aggressive interactions such as rearing or sniffing. Finally, it is also worth mentioning that chronic treatment with a variety of antidepressant drugs increases aggression in the resident–intruder paradigm (Mitchell, 2005), suggesting that this may constitute a model of antidepressant-induced mania in individuals with BD (Koszewska and Rybakowski, 2009). …”

Anticholinergic Mechanisms

“…In our recent retrospective analysis of antidepressantinduced mood conversion to mania/hypomania in patients treated from 1972-1996 in the Affective Disorder Unit, Institute of Psychiatry and Neurology, in Warsaw, Poland, we have demonstrated a significantly higher percentage of the switch in patients treated with TCAs than with non-TCA antidepressants. 12 Furthermore, within TCA drugs, the frequency of switch showed some correlation with the affinity of the drug to muscarinic receptors. The frequency of switch in our study was highest in patients who received amitriptyline (42%), the drug with a Kd (equilibrium dissociation constant for muscarinic acetycholine receptors in human brain) of about 18, 2 and lowest in those who received desipramine (18%), which has a Kd of about 198.…”

The Pharmacological Treatment of Bipolar Disorder: The Question of Modern Advances

“…34−36 Antidepressants, either as monotherapy or in combination with lithium, have been shown efficacious for depression in bipolar disorder, 37 although a trial by Sachs and colleagues 38 reported no statistical difference between a group that received augmenting antidepressant to a "mood stabilizer" (lithium, valproate, carbamazepine, or an atypical antipsychotic) versus a group that received the "mood stabilizer" plus placebo. The common perception is that antidepressants (and more with tricyclics than with non-tricyclics) carry a risk of switching the person into mania, 39 but some critical literature reviews suggest that this risk may be overstated. 40,41 For patients with depression with psychotic symptoms, antipsychotic medications would be added.…”