Treatment Considerations
This case also highlights several psychotherapy and psychopharmacology treatment considerations for patients with a predominantly negative and cognitive symptom presentation. The veteran was initially difficult to engage in psychotherapy. Although patients with SSDs often have difficulty engaging in treatment, patients with a predominant negative and cognitive symptom profile may experience more difficulty doing so.10 Previous research suggests that both negative symptoms and cognitive symptoms are inversely related to treatment engagement.11,12
By their very nature, negative symptoms may make it difficult to fully engage in psychotherapy. First, avolition and amotivation likely make it difficult for patients to attend psychotherapy appointments. Furthermore, negative symptoms may make it difficult to emotionally engage with the content of psychotherapy, thus limiting the potential benefits. Cognitive symptoms may also make it more difficult for patients to fully reap the benefits of psychotherapy. Deficits in attention, memory, and abstract reasoning seen in other mental health and medical conditions are associated with poorer treatment outcomes in psychotherapy.13,14 Thus, it may be especially difficult to engage patients with primarily negative and cognitive symptoms of SSDs in psychotherapy. However, given the link between these symptoms and functional impairment, it is even more important to evaluate and address such barriers to treatment.
This case highlights the utility of clozapine in the treatment of SSDs. Many commonly prescribed antipsychotic medications have questionable efficacy in treating negative symptoms, and none of the currently available antipsychotics are approved for this indication.15 In our case, the veteran saw a limited reduction of her negative or cognitive symptoms from her use of olanzapine. However, case reports, naturalistic follow-up, and open-label studies suggest that clozapine may be efficacious in targeting negative symptoms of SSDs.16-19 Previous research also suggests clozapine is more effective than other antipsychotic medications, including olanzapine, quetiapine, and risperidone, in decreasing overall SSD symptoms.20,21 Additionally, there is initial evidence of the efficacy of clozapine in treating cognitive symptoms, suggesting that some areas of cognition may improve in response to this medication.22-24 On the other hand, a recent case study suggests high doses of clozapine may be associated with cognitive impairment, although cognitive impairment was still greater without medication than at this higher dose.25 Thus, further research is needed to refine our understanding of the impact of clozapine on cognitive symptoms in SSDs.
Despite the promising research behind clozapine, it remains widely underprescribed, likely due to concerns regarding the potential adverse effects.26,27 Clozapine has been associated with many adverse effects, the most concerning being neutropenia, which can lead to serious infection and death. Thus, one concern among clinicians may be the potential lethality of clozapine. However, a wealth of research indicates clozapine can be safely administered under medical supervision.26,28 In fact, clozapine has been linked to lower all-cause mortality rates and lower mortality rates by suicide compared with other antipsychotic medications.29-31 It may therefore be argued that clozapine lowers the overall risk of mortality. Prescribers may also be weary of adherence to regular blood tests that patients must undergo to monitor their risk for neutropenia. This is the most frequently cited anticipated barrier to beginning a trial of clozapine.27 These concerns may not be unfounded; indeed, if avolition and amotivation make it difficult to attend psychotherapy sessions, these factors may logically make it difficult to attend blood draw appointments. In response to such barriers, several solutions have been suggested regarding potential blood draw nonadherence, including the use of in-home treatment teams and point-of-care monitoring.32,33
Conclusions
Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for patients with such presentations. As our case highlights, patients with such presentations may often be misdiagnosed, as negative and cognitive symptoms may be attributed to other disorders. Additionally, patients with this presentation may experience difficulty engaging in psychotherapy and may not see the same benefits from common antipsychotic medications as patients with predominantly positive symptoms. Clozapine emerges as a promising treatment for addressing negative and cognitive symptoms, although it remains widely underutilized. In cases where clinicians encounter patients with predominantly negative and cognitive symptoms, we strongly recommend consultation and referral to psychiatric care for medication management.
The current case highlights the need for individually tailored treatment plans for individuals seeking mental health care. Clinicians of patients with any mental disorder, but especially those with SSDs of predominantly negative and cognitive symptoms, should carefully formulate a treatment plan based on relevant case history, presentation, and current empirical literature. A singular, one-size-fits-all approach should not be universally implemented for such patients. Our case demonstrates how careful multidisciplinary evaluations, review of medical records, collateral information from patients’ family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.
Acknowledgments
A.K. is supported by the US Department of Veterans Affairs Office of Academic Affiliations Advanced Fellowship Program in Mental Illness Research and Treatment, the Central Texas Veterans Affairs Health Care System, and the VISN 17 Center of Excellence for Research on Returning War Veterans.