APA 2021: Antidepressants in treatment-resistant unipolar and bipolar depression

The combination of antidepressants (AD) and antipsychotics (AP) and / or mood stabilizers (MS) generates a greater clinical response in treatment-resistant unipolar depression (TRD-UP) than in depression treatment-resistant bipolar (TRD-BD), and no clinical benefit was seen by adding AD to TRD-BD regimens, according to study results presented at the American Psychiatric Association annual meeting, held virtually from May 1 to 3, 2021.

Although the use of AD to treat TRD-BD is common, due to the theoretical continuum between TRD-UP and TRD-BD, the practice is nonetheless controversial. Study researchers sought to compare the response to the combination of AD and MS and / or PA in 76 patients with TRD-UP versus 70 patients with type 1 TRD-BD. and 60 of TRD-BD type 2, with the secondary objectives of (1) comparing the clinical TRD-BD trajectory, with or without AD treatment, and (2) testing a differential response to AD between the sub- types of TRD-BD

The Hamilton Depression Rating Scale (HAMD) scores at the start of treatment (T0) and after 3 months (T3) were compared; score changes were analyzed and delta scores for specific treatment combinations were calculated and compared using independent samples t-tests.

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Among patients treated with AD, TRD-UP patients showed higher HAMD scores than TRD-BD (F1,139= 34.54; P <.001 not>p2= 0.20), and yet TRD-UP patients nevertheless showed a greater improvement from T0 to T3 (F1,139= 8.88; P = 0.003; notp2= 0.06). Greater reductions in HAMD were generated with AD + AP in TRD-UP vs TRD-BD (t= 2.48; P = 0.02; re= 0.58). In TRD-UP compared to TRD-BD, trends for greater improvement were seen with AD + MS (t= 1.81; P = 0.07; re= 0.58) and AD + AP + MS (t= 1.9; P = 0.05; re= 0.55). The addition of AD to treatment with PA alone or with MS did not change the TRD-BD clinical trajectory (F1,122= 0.67; P = 0.41; notp2= 0.00), nor did it provide any additional benefits within BD subtypes.

The study researchers concluded: “The AD + AP / MS combination generates a greater clinical response in TRD-UP than in TRD-BD supporting the existence of a distinct neurobiological profile in TRD-UP compared to TRD. -BD. Our results also highlight the lack of clinical benefit for adding AD to TRD-BD. “


Moderie C, Nuñez N, Comai S, Gobbi G. Distinct effects of antidepressants in treatment-resistant unipolar and bipolar depression in combination with mood stabilizers and antipsychotics. Presented at the APA Annual Meeting May 1-3, 2021. Abstract / Poster 5271.

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