Psychopharmacology Strategies for Mood Disorders

Combination Therapy

The American Academy of Child and Adolescent Psychiatry identifies combination therapy as using medications together from the outset or adding medications to treat separate, co-occurring conditions, such as using a stimulant plus an SSRI for comorbid ADHD and anxiety 1, 2
Combination therapy may be used to address side effects of an effective primary agent, such as adding benztropine for extrapyramidal symptoms caused by an antipsychotic 1, 2
The American Academy of Child and Adolescent Psychiatry recommends using combination therapy to sculpt medication coverage, such as using two formulations of the same medication class to extend therapeutic coverage throughout the day 1, 2

The American College of Physicians defines augmentation therapy as adding a second medication to boost the effectiveness of a partially responsive first-line treatment for a single disorder, such as adding lithium to ongoing antidepressant treatment for treatment-resistant depression 3, 4
Augmenting citalopram with bupropion or buspirone may be considered when the initial SSRI produces inadequate response 3, 4
The American College of Physicians recommends adding atypical antipsychotics, such as risperidone or aripiprazole, to SSRIs in treatment-resistant OCD, where approximately one-third of SSRI-resistant patients show clinically meaningful response 3, 4

Before implementing either combination or augmentation strategy, clinicians must verify that the initial treatment trial was adequate in dose, duration, and adherence, typically 8-12 weeks at maximum tolerated doses for SSRIs in depression 2
The American Academy of Child and Adolescent Psychiatry warns against using two antidepressants or two antipsychotics as an initial treatment approach or specific endpoint without empirical support 1, 2
When using antipsychotic augmentation, mandatory monitoring includes weight gain, blood glucose, and lipid profiles for metabolic side effects, as well as assessment for serotonin syndrome when combining serotonergic medications 5

Switching to a different medication represents an alternative to augmentation when initial monotherapy fails, with no significant difference in response or remission when switching between SSRIs, such as bupropion vs. sertraline vs. venlafaxine 3, 4
The American College of Physicians found no difference in response or remission when switching to cognitive therapy versus switching to another SSRI 3, 4

The American College of Physicians recognizes lurasidone as an atypical antipsychotic approved for augmentation therapy in bipolar depression, with a moderate efficacy as adjunctive therapy to lithium or valproate 6, 7, 8

The American Academy of Child and Adolescent Psychiatry recommends assessing for serotonin syndrome when combining serotonergic medications, such as venlafaxine, with antipsychotics, and monitoring for agitation, confusion, tremor, hyperthermia, and autonomic instability 9

The American Academy of Child and Adolescent Psychiatry suggests considering prophylactic or as-needed benztropine if extrapyramidal symptoms emerge when using lurasidone, which can cause akathisia, extrapyramidal symptoms, and somnolence 9

The American Academy of Child and Adolescent Psychiatry recommends monitoring depressive symptom improvement, akathisia, extrapyramidal symptoms, somnolence, weight, and metabolic parameters at 2-4 week intervals when initiating lurasidone, and adjusting doses of CYP3A4 interacting medications if present 9