Release date 2024.9.24
In March 2024, Oliva et al. reported a comparison of the efficacy of drug treatments for psychotic depression 1).
In this study, when considering only efficacy, including sub-analyses, it was shown that amoxapine (Amoxan), imipramine (Tofranil), and amitriptyline (Tryptanol) were superior when used as monotherapy.
In combination therapy with antidepressants and antipsychotics, including sub-analyses, amitriptyline + perphenazine (Trilafon) and venlafaxine (Effexor) + quetiapine (Seroquel) were shown to be superior.
In June, Taipale et al. reported a comparison of the efficacy of drug treatment in the maintenance therapy of psychotic depression 2).
Since psychotic depression carries a high risk of relapse and maintenance therapy is essential, this new report, combined with Oliva’s findings, represents valuable information.
The primary outcome measure was set as the reduction in hospital readmission rates.
Compared to not using antidepressants, the following three antidepressants were associated with a lower risk of relapse (Figure 1):
- Bupropion (Wellbutrin)
- Vortioxetine (Trintellix)
- Venlafaxine (Effexor)
（Fig 1）Comparison of the Efficacy of Antidepressant Monotherapy in Maintenance Treatment for Psychotic Depression
Among antipsychotic monotherapy, long-acting injectable antipsychotics (not restricted by specific drugs) and clozapine (Clozaril) were associated with a lower risk of relapse.
In combination therapy with antidepressants and antipsychotics, the following combinations were associated with a lower risk of relapse (Figure 2):
- Amitriptyline (Tryptanol) + olanzapine (Zyprexa)
- Sertraline (Zoloft) + quetiapine (Seroquel)
- Venlafaxine (Effexor) + quetiapine (Seroquel)
（Fig 2）Comparison of the Efficacy of Combined Antidepressant and Antipsychotics Therapy in Maintenance Treatment for Psychotic Depression
Even compared to the combination of antidepressants and antipsychotics, bupropion and vortioxetine were associated with a reduction in the risk of relapse.
The efficacy of drugs compared to not using either antidepressants or antipsychotics was as follows (Figure 3):
（Fig 3）Comparison of the Efficacy of Medications in Maintenance Treatment for Psychotic Depression
The authors noted that escitalopram was not associated with a reduction in the risk of relapse in psychotic depression, and they recommended avoiding its use.
Additionally, mirtazapine (Remeron) was found to be associated with an increased risk of relapse.
Bupropion inhibits the reuptake of norepinephrine and dopamine, thereby increasing dopamine activity. The authors discussed the possibility that enhancing dopamine activity may be effective in improving psychotic depression.
Vortioxetine, sertraline, and venlafaxine all have effects on dopamine, supporting this hypothesis.
In practice, it is believed that improving reduced dopamine activity in the prefrontal cortex with antidepressants and controlling excessive dopamine activity in the mesolimbic system, which is related to psychosis, with antipsychotics helps stabilize overall dopamine activity in the brain, leading to the improvement of psychotic depression.
Since vortioxetine was not included in Oliva’s study, the result that it was associated with a reduction in the risk of relapse as monotherapy is noteworthy, especially considering that most guidelines recommend combining antidepressants with antipsychotics.
References
- 1） Oliva V, et al.: Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis. Lancet Psychiatry, 11: 210-220. 2024.
- 2） Taipale H, et al.: Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts. World Psychiatry, 23: 276-284, 2024.
Column list
- Characteristics, Mechanism of Action, and Side Effects of Zuranolone
- Characteristics, Mechanism of Action, and Side Effects of Auvelity
- Characteristics, Mechanism of Action, and Side Effects of Esketamine
- Latest Comparison of Weight Changes Due to Antidepressants
- Comparison of the Efficacy of Long-Acting Injectable Antipsychotics in Acute Schizophrenia: Latest Report
- Comparison of Efficacy and Tolerability of Drug Treatments in Acute Manic Episodes of Bipolar Disorder: Latest Report
- Comparison of the Efficacy of Drug Treatment in Maintenance Therapy for Psychotic Depression
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