Do medications help or hinder benefits of psychosocial interventions to improve cognitive and social difficulties in schizophrenia?

Schizophrenia is best treated holistically with medication and psychosocial interventions such as cognitive enhancement therapy (CET) and social skills training (HOPES)—the interventions included in Project SUCCESS.  Clinicians and clients often believe that these interventions are simply additive. It is important to realize, however, that psychosocial and pharmacological interventions are more than the sum of their parts. In other words, they are synergistic. I will outline here two key considerations that clinicians will do well to keep in mind.

First, our work has shown that psychosocial interventions such as CET work best when psychosis is adequately stabilized by antipsychotic medications. It Is therefore important to pay careful attention to continuing psychotic symptoms such as delusions and hallucinations and appropriately treat them with antipsychotics and mood stabilizers.

Second, we have also found that medications, if not used properly, can hinder progress in improving cognitive abilities and community function. For example, anticholinergic drugs such as benzhexol and trihexyphenidyl, if used in larger than needed doses can impair memory and cognitive functions. These medications help to counter Parkinson-like side effects of antipsychotics, but their long-term use can be counterproductive.   Additionally, some antipsychotics such as olanzapine and clozapine, and some antidepressants such as amitriptyline have anticholinergic properties themselves and can compound this problem. We are not arguing against their use, as they can be very helpful, even lifesaving. However, clinicians should avoid unnecessary polypharmacy, e.g. simultaneously combining two or more drugs which have anticholinergic effects (e.g. olanzapine and antihistamines such as diphenhydramine, or Benadryl). 

A frequent question clients and clinicians ask is whether there are medications to reliably treat cognitive impairments in schizophrenia. Unfortunately, there are none. On the other hand, simplifying the medication regime by subtracting certain medications from the prescription regimen when they are no longer needed (for example, anticholinergic drugs), can go a long way to improving cognition in many patients and maximizing the benefit of psychosocial programs like CET and HOPES. 

Eack SM, Wojtalik JA, Keshavan MS. Anticholinergic medications in the treatment of psychoses: Pharmacological subtraction is better than addition. Schizophr Res. 2023 Dec;262:40-41. 

Matcheri S. Keshavan MD

Stanley Cobb Professor and Academic Head of Psychiatry,

Beth Israel Deaconess Medical Center and

Massachusetts Mental Health Center,

Harvard Medical School

Editor, Schizophrenia Research