Is it safe to take Abilify (aripiprazole) and Risperdal (risperidone) together?

Safety of Combined Aripiprazole and Risperidone Therapy

The combination of aripiprazole (Abilify) and risperidone (Risperdal) is generally not recommended as first-line treatment due to increased side effect burden without clear evidence of improved efficacy.

Guidelines on Antipsychotic Polypharmacy

• Most clinical guidelines recommend antipsychotic monotherapy as the preferred approach for treating psychotic disorders 1.
• The National Institute for Health and Care Excellence (NICE) advises against regular combined antipsychotic medication except for short periods when changing medications 1.
• The World Federation of Societies of Biological Psychiatry guidelines only recommend considering antipsychotic polypharmacy in specific cases like treatment-resistant schizophrenia 1.
• The American Psychiatric Association guidelines endorse monotherapy and do not acknowledge situations where antipsychotic polypharmacy would be recommended 1.

Risks of Combining Aripiprazole and Risperidone

• Both medications are antipsychotics that work through dopamine receptor modulation, but with different mechanisms - aripiprazole is a partial D2 agonist while risperidone is a D2 antagonist 1.
• This combination may lead to:
  • Increased extrapyramidal symptoms (EPS) due to additive effects on dopamine receptors 1.
  • Potential for severe psychotic exacerbation in some patients due to aripiprazole's partial agonist activity at D2 receptors 2.
  • Higher global side-effect burden, including increased risk of Parkinsonian side effects 1.
  • Potential cognitive impairment, though this may be related to higher total antipsychotic dosing rather than polypharmacy itself 1.

Evidence on Efficacy

• A multicenter, randomized, double-blind, placebo-controlled study found that adding aripiprazole to risperidone did not improve psychiatric symptoms compared to risperidone alone 3.
• The only significant benefit observed was decreased prolactin levels when aripiprazole was added to risperidone (-18.7 ng/mL vs -1.9 ng/mL with placebo; P<0.001) 3.

Specific Situations Where Combination May Be Considered

• For treatment-resistant schizophrenia where clozapine monotherapy has failed, adding a second antipsychotic might be considered 1.
• When managing medication side effects, particularly when aripiprazole is added to counteract metabolic or prolactin-related side effects of other antipsychotics 1, 3.
• During cross-titration periods when switching from one antipsychotic to another 1.

Practical Recommendations

• If antipsychotic monotherapy is ineffective, consider optimizing the dose of a single agent before adding a second antipsychotic 1.
• If polypharmacy is deemed necessary, select antipsychotics with differing side-effect profiles to minimize additive adverse effects 1.
• Monitor closely for:
  • Extrapyramidal symptoms 1
  • Sedation 4
  • Metabolic effects 1
  • Potential worsening of psychotic symptoms 2
  • Drug-drug interactions affecting plasma concentrations 1

Conclusion

While the combination of aripiprazole and risperidone is sometimes used in clinical practice, the evidence does not support routine use of this combination. Antipsychotic monotherapy should be optimized first, with careful consideration of the risk-benefit ratio before initiating polypharmacy.