Mental illness is on the rise in today’s ever-changing society. Mental illnesses can be some of the most disturbing and upsetting to family members and patients. Many family members can lose sight of the person that once was, as a person’s brain chemistry can absolutely destroy their personality. One of the most destructive and devastating diseases is schizophrenia. Schizophrenia is quite complex, and it can present with a vast array of symptoms. Patients can present with various delusions, and can often have other manifestations of those delusions. Patients can feel paranoid, scared, and this can all present as disorganized thoughts or speech. Patients with schizophrenia are classified to have both positive and negative symptoms. Negative symptoms occur due to deficits in a person’s mental capacity. These symptoms can present as lack of cognition, inability to pay attention, and lack of memory. These symptoms can be thought to be a deficit in brain function. Patients can also have positive symptoms with schizophrenia. Positive symptoms can be thought of as hyperactivity of the brain. This can manifest as delusions, paranoia, and hallucinations. Although these are thought to be the “typical” schizophrenia symptoms, both are classic for a schizophrenia diagnosis. Unlike other mental health diseases, schizophrenia treatment is unpredictable in terms of response rates. Only about 20% of patients report satisfaction with their schizophrenia regimen. Some of the most classic medications with benefit in patients with schizophrenia are the second-generation antipsychotics. Olanzapine, the generic for Zyprexa, is a second generation antipsychotic. It has been proven effective for patients, but the unfavorable weight gain associated with olanzapine has hindered patient adherence and satisfaction. This weight gain is the most significant of the second-generation antipsychotics, along with clozapine. New strategies have been developed to address this issue.(1)
A new medication was recently granted FDA approval for the management of weight when patients are being treated with olanzapine. In addition to the olanzapine to manage schizophrenia, there is another component added to the medication to help subside weight gain. Olanzapine/samidorphan was approved by the FDA in May 2021. It contains the second generation antipsychotic and an opioid receptor antagonist to curve the associated weight gain. Samidorphan works similarly to naltrexone in curving weight gain. It is contraindicated in patients with opioid use disorders or those undergoing opioid addiction withdrawal. Patients should also avoid treatment if there is active opioid use for chronic or acute pain management. In patients on short-acting opioids, there should be a 7 day period before use of olanzapine and samidorphan. In patients using long-acting opioids for pain management, there should be a minimum of 14 days before use.
When thinking about increasing patients’ gaps in care and adherence, addressing burdensome side effects is one of the main strategies. Of course, with adding a new medication comes new side effects. It is important to weigh the risks and benefits of starting a new medication with patients and families. Patients with severe schizophrenic symptoms must be appropriately treated, and addressing weight gain is a very important strategy to increase adherence.
References:
Patel KR, Cherian J, Gohil K, Atkinson D. Schizophrenia: overview and treatment options. P T. 2014;39(9):638-645.
Lybalvi. Package insert. Alkermes; 2021.
Schizophrenia
Schizophrenia is among the most intricate and demanding psychiatric conditions, characterized by a diverse array of symptoms including disorganized and unusual thinking, delusions, hallucinations, inappropriate emotional responses, and disrupted social functioning. Schizophrenia impacts about 24 million individuals globally, equivalent to 1 in 300 people (0.32%). Among adults, this prevalence increases to 1 in 222 people (0.45%). While less common than many other mental health disorders, schizophrenia typically emerges in late adolescence or early twenties, often manifesting earlier in men than women. This disorder is commonly linked with substantial distress and impairment across various aspects of life including personal, family,, educational and occupational domains. Although research has not identified a single cause of schizophrenia, it is believed to result from the interaction between genetic predispositions and a variety of environmental factors.
The pathophysiology of schizophrenia involves complex and multiple molecular and neural circuit changes. Neurotransmitter imbalances are key to understanding the pathophysiology of schizophrenia, with dopamine, serotonin, glutamate, and gamma-aminobutyric acid (GABA) all playing significant roles. Excessive dopamine activity in the mesolimbic pathway, which extends from the ventral tegmental area to the limbic regions, is believed to contribute to the positive symptoms of schizophrenia. Conversely, reduced dopamine levels in the mesocortical pathway, connecting to the ventral tegmental area to the cortex, may be responsible for negative symptoms and cognitive deficits. Moreover, the nigrostriatal pathway is associated with extrapyramidal motor side effects caused by D2 receptor blockers, while the tuberoinfundibular pathway is linked to the hyperprolactinemia observed with the use of these blockers.
Treatment Overview:
To diagnose schizophrenia, a comprehensive evaluation is essential, including a detailed mental status examination, psychiatric diagnostic interview, physical and neurologic examinations, complete family and social history, and laboratory tests to rule out any general medical or substance-induced causes of psychosis. Both first-generation antipsychotics, also referred to as traditional and second-generation antipsychotics (atypical) are utilized in treating schizophrenia. While second-generation antipsychotics generally produce minimal or no extrapyramidal symptoms (EPS) compared to first-generation antipsychotics, they also have a lower likelihood of causing tardive dyskinesia and do not significantly affect serum prolactin levels. However despite the reduced risk of neurological effects, second-generation antipsychotics are associated with increased metabolic side effects such as weight gain, hyperlipidemia, and diabetes mellitus.
Stage 1a of the treatment algorithm targets patients experiencing their initial acute episode of schizophrenia. Among second-generation antipsychotics (SGAs), aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone demonstrate efficacy in first-episode patients, with lurasidone showing effectiveness in adolescents with schizophrenia, although most were not treatment naive. Quetiapine, associated with significant weight gain, is not recommended by certain guidelines, thus highlighting aripiprazole, risperidone, and ziprasidone as preferable options for first episode patients (Stage 1a). Stage 1B is geared towards patients who were previously treated with an antipsychotic and therapy is being restarted because the patient stopped taking the medication If significant symptom improvement and good tolerability are observed during the initial antipsychotic trial and the patient wishes to continue with the same medication, it may be restarted. Should an alternative medication be necessary, one from stage 2 should be considered.
Stage 2 pertains to those patients who did not achieve satisfactory clinical progress with the antipsychotic administered in stage 1A or 1B, or those who initially responded but experienced a recurrence of symptoms while on medication. In this stage, the recommendation is monotherapy with either a first-generation antipsychotic or a second-generation antipsychotic which was not previously used in stage 1 or 1B. Clozapine is generally not advised at this stage due to safety concerns and the requirement for monitoring white blood cell (WBC) levels. However, it should be considered for patients exhibiting suicidal tendencies due to its efficacy in reducing suicidal behavior. Clozapine may also be an option for those patients with a history of violence or concurrent substance abuse. If a patient experiences intolerable side effects with the antipsychotic prescribed in stage 1A, 1B, or stage 2 an alternative antipsychotic therapy for that particular stage should be selected.
While schizophrenia poses significant challenges within the realm of psychiatric disorders, there are a range of medications that have demonstrated efficacy in managing symptoms. Effective management of schizophrenia entails adherence to prescribed medications, regular healthcare appointments, prompt symptom recognition, avoidance of alcohol and recreational drugs, and seeking support from organizations. These actions are crucial for optimizing treatment outcomes and improving quality of life for individuals living with schizophrenia.
References:
professional, C. C. medical. (n.d.-b). Schizophrenia: What it is, causes, symptoms & treatment. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/4568-schizophrenia
Hany, M. (2024, February 23). Schizophrenia. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK539864/
Crimson, M. L., Smith, T., & Buckley, P. F. (n.d.). Schizophrenia. Shibboleth authentication request. https://accesspharmacy-mhmedical-com.jerome.stjohns.edu/content.aspx?sectionid=224358695&bookid=2577&Resultclick=2#1182457413