Antidepressant combination versus antidepressants plus second-generation antipsychotic augmentation in treatment-resistant unipolar depression

Abstract

Patients with treatment-resistant unipolar depression (TRD) are treated with antidepressant combinations (ADs) or with second-generation antipsychotics plus AD (SGA+AD) augmentation; however, the clinical characteristics, the factors associated independently with response to SGA+AD, and the outcome trajectories have not yet been characterized. We performed a naturalistic study on the latest stable trial (medication unchanged for about 3 months) in 86 TRD patients with resistance to at least two ADs trials, who received ADs (n=36) or SGA+AD (n=50) treatments. Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton-Depression Rating Scale (HAM-D17), and other scales were administered before (T0) and after the latest 3-month stable trial (T3). Compared to ADs, the SGA+AD group showed increased percentage of depression with psychotic features, comorbidity for personality disorders and substance use disorders (SUD), higher number of failed ADs pharmacotherapies and depressive symptoms at T0 on all scales (P<0.001). Compared to T0, both treatments significantly decreased depressive symptoms on MADRS and HAM-D17 at T3 (P<0.001); however, the SGA+AD augmentation produced a greater decline in mean score. Logistic regression analysis indicated that psychotic features, personality disorders, and SUD were independently associated with SGA+AD treatment. Given the greater improvement in depression following SGA+AD augmentation, SGA augmentation should be indicated as a first-line treatment in severe TRD with psychotic features, SUD, and personality disorders.

Clinical correlates of augmentation/combination treatment strategies in major depressive disorder

“…Whereas our patient sample was not itemized according to the different applied augmentation/combination strategies, clinical characteristics of treatment‐resistant MDD patients receiving antidepressant combination medication were compared to those treated with SGA augmentation in a naturalistic study of Gobbi et al . The authors found psychotic features, various comorbidities, high depressive symptom severity, and a high degree of treatment resistance to be associated with the add‐on prescription of SGAs.…”

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

“…First-line pharmacological treatments in unipolar depression, anxiety, PTSD, and OCD revolve around selective serotonin reuptake inhibitors (SSRIs) [such as fluoxetine, fluvoxamine, citalopram and paroxetine, which inhibit serotonin (5-HT) reuptake at the synapse] and serotonin-norepinephrine reuptake inhibitors (SNRIs) [such as clomipramine, venlafaxine, duloxetine, milnacipran, and levomilnacipran, which inhibit 5-HT and norepinephrine (NE) reuptake at the synapse]. Second-line treatments include the second-generation (atypical) antipsychotics acting on 5-HT 2A , 5-HT 1A , and D2 receptors (Gobbi et al, 2018). In some cases, tricyclic antidepressants (such as imipramine and amitriptyline, which also inhibit monoamine reuptake) are similarly, or more, effective for the treatment of some patients, especially in hospitalized patients with severe depression (Bauer et al, 2002;Bandelow et al, 2008).…”

Augmentative Pharmacological Strategies in Treatment-Resistant Major Depression: A Comprehensive Review

“…Gobbi and collaborators [ 56 ] reported that both the augmentation with another AD or with a SGA (olanzapine, risperidone, quetiapine, aripiprazole) improved depressive symptoms over time; hovewer, SGAs performed better than Ads ( Table 2 ).…”