Lynchburg Journal of Medical Science

Lynchburg Journal of Medical Science




Nancy Reid, MHA, DHSc, PA-C




To discuss the importance of 1). Closely monitoring antipsychotic treatment and 2) identifying psychosocial factors that will affect medication compliance before patients are diagnosed with Treatment-Resistant Schizophrenia (TRS).

To offer a brief overview of available treatments for TRS.

Search Method:

Pertinent studies were found via the Cochrane Schizophrenia Group Trials Register, PubMed, and Medline. Searched for clinical trials, clinical review and systematic review journals. Utilized keywords: treatment-resistant schizophrenia, diagnosis, treatment, antipsychotics. Ran searches from May 2002 to January 2019. Checked for additional journal articles in reference lists of included review articles. The searches yielded 18 articles.

Selection Criteria:

Selected articles that discussed the relevant guidelines for the diagnosis and management of TRS. Also, I selected articles that focus on the challenges a clinician has in diagnosis and treating the TRS patient. Three systematic reviews and ten clinical reviews met the selection criteria for inclusion in this review.

Data Collection and Analysis:

Reviewed and selected data from the included articles. Focused on articles that discuss the diagnosis and treatment of TRS.

Main Results:

Diagnosing and treating TRS is challenging for mental health care clinicians due to the different domains that affect the patient’s treatment compliance. These domains include side effects, negative schizophrenia symptomatology, and psychosocial factors such as inadequate social support. Once a mental health clinician ascertains that patient has a TRS diagnosis, treatment can also be challenging. Clozapine remains the gold standard treatment for TRS,1,2 but when it fails, clinicians can use other drug agents and psychological interventions for clozapine augmentation. A controversial topic regarding TRS is the use of one antipsychotic versus multiple antipsychotic agents. There have been very few studies comparing the use of monotherapy against combined antipsychotic treatments. Barbui et al. presented a systematic review on this topic. A clinically randomized trial showed that combined antipsychotic yielded benefits from modest to none.


TRS is a challenging problem for mental health clinicians and the team who cares for them because multiple factors make this condition difficult to diagnose and treat. In order to diagnose patients, medication compliance must be closely monitored. Also, the team must identify psychosocial factors that may hinder patients from being compliant with treatment. Many psychiatric providers attempt to treat patients with combined antipsychotic medications, but current studies are small and limited. So far, these studies indicate little or no benefit compared to monotherapy treatment.


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