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S061-3

Combination Therapy for Treatment-Resistant Depression with Antipsychotics or
Other Agents

Ken Inada

Department of Psychiatry, Tokyo Women’s medical university, Japan

Background/Objective: There are several options for treating treatment-resistant depression (TRD)
such as combination therapies with antidepressant and antipsychotics, mood stabilizers,
benzodiazepines, or dopamine agonists. Evidence of the efficacy and tolerability of these drugs vary
in each study.

Second generation antipsychotics are well studied in a number of well-controlled studies,
meta-analyses, and practical clinical studies. Evidence shows that combination therapies with
antidepressants and aripiprazole, olanzapine, quetiapine, or risperidone are more effective than a
combination of antidepressants and placebo. However, combination therapies have particular adverse
properties that may prompt the patients to discontinue them.

Benzodiazepines are effective for the initial treatment of depression and to reduce patient dropout
rates, but there is no evidence that they are effective for treating TRD.

It is rational to use drugs with different pharmacodynamics or mechanisms in combination therapies.

Method: We have studied the mechanisms of various classes of psychiatric drugs in preclinical
settings focusing on the dynamic changes in dopamine.

Result: From the results of our study, psychiatric drugs have similar effects on dopamine release in
response to psychological stress, but have different effects on basal dopamine release. These results
may be helpful in choosing the appropriate drugs or for the development of next-generation
antipsychotic agents.

Conclusion: Combination therapies with different antipsychotic agents, which have different
mechanisms, are effective and rational, but their risks and benefits should be carefully considered
before treatment.