Strategies to Manage Adverse Effects From Schizophrenia Treatment

In this video, Christoph Correll, MD, professor of psychiatry and molecular medicine, Zucker School of Medicine at Hofstra/Northwell, New York, offers clinical guidance for managing adverse affects from schizophrenia treatment, including weight gain and movement disorder. Dr Correll describes strategies ranging from adjunctive medications to lifestyle interventions.

Don't miss these other clinical pearls from Dr Correll:

>>Beyond D2 Receptor Manipulation: Novel Agents for Schizophrenia Treatment

>>Recognizing the Early Indicators of Schizophrenia

For more expert insights, visit the Schizophrenia Excellence Forum right here on Psych Congress Network.

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Read the Transcript

Psych Congress Network (PCN): Could you elaborate on some of the most common side effects of second-generation antipsychotics and their impact on patient wellbeing and treatment adherence?

Christoph Correll, MD: Second-generation antipsychotics are defined by having dopamine receptor blockade or partial agonism postsynaptically, but they also hit some other receptors that are associated with either efficacy or reduced parkinsonian symptoms. That's like the serotonin blockade. These medications have been foundational and an advancement over the first-generation agents that just blocked dopamine too much, without countering other effects. But they still have certain side effects. There's a possibility of still EPS at higher doses, parkinsonism, tardive dyskinesia, also akathisia. The postsynaptic dopamine blockade with some agents can lead to prolactin elevation, which can lead to sexual side effects. There can be sedation when you dampen the dopamine tone. There can be secondary negative and cognitive symptoms when there's sedation or EPS. There's also the possibility of weight gain and metabolic abnormalities, dyslipidemia, diabetes.

Again, these medications are not all created equal. They have different liabilities and one or another area, but these side effects exist, and they are not just physical or nuisance variables. They also affect patients' wellbeing and patients' functioning. When patients were asked on a scale from zero to a hundred, with a hundred being fully impaired in your functioning, and zero no impairment, about activating or sedating side effects and about weight gain and sexual side effects, they ranked these side effects of impairing their functioning in the high fifties to high sixties. That's unfortunately then also sometimes related to non-adherence because patients feel that they're dumbed down, they're in a brain fog, that they can't enjoy things as much anymore, and also that they have weight gain and physical abnormalities.

PCN: Can you share some examples of adjunctive medications, as well as lifestyle interventions, that are commonly used to manage specific side effects of atypical antipsychotics? Then how do you determine when to prescribe them?

Dr Correll: In terms of augmentation strategies to reduce side effects, I think what comes to mind for most clinicians is, "Oh, I use an anticholinergic when there's EPS." Please don't. Don't mask EPS because that can cause with the anticholinergic cognitive dysfunction and bring out a higher risk of tardive dyskinesia. Try to stay below the neuroleptic threshold, change the medication dose or the medication type. But what about the cardiometabolic side effects? Weight gain, dyslipidemia, glucose abnormalities, hypertension? Well, we can add non-pharmacologic treatment options, like healthy lifestyle intervention, but it's hard to do. It's even hard for us to exercise and diet appropriately. You can also add metformin. This is one agent that has been shown to reduce the weight to a degree when you add it with antipsychotics. Might also help with some insulin sensitivity improvement. But it's not a very big effect.

What's now really big are GLP-1 agonists, G-protein-like receptor agonists that have been helpful in improving diabetes, but also reducing body weight in people without anti-psychotics and without mental illness. There are some data with liraglutide augmentation, but that's one weekly subcutaneous treatment, that it really reduces weight quite a lot, maybe twice to three times as much as with metformin. Now there is semaglutide, which is approved and could also be used. There are less data available in people with schizophrenia or bipolar disorder, who are on anti-psychotics. Then there is a recently approved drug combination, which is olanzapine and samidorphan together, which also leads to less weight gain than olanzapine alone. It's approved for the treatment of schizophrenia or bipolar I disorder. In sub-analysis that we performed looking at patients without metabolic syndrome, it also reduced over six months metabolic syndrome, cut it down by 50%, hypertension, new-onset hypertension, as well as an increase in five-centimeter waist circumference.

PCN: What specific monitoring practices do you employ to assess the occurrence and severity of adverse effects in patients taking atypical antipsychotics?

Dr Correll: We're in medicine. When we treat patients, we need to monitor. We need to monitor the benefits and the potential risks. That means we ask patients how they're doing. We might use some questionnaires for the efficacy. We maybe ask informants. But for side effects, we also need to ask. We need to educate patients what side effects they might expect and do some monitoring. For example, for extrapyramidal side effects, do a Simpson-Angus exam, just moving the joints where there can be stiffness. For tardive dyskinesia risk, please do an AIMS exam and a normal involuntary movement exam. These two together take two to three minutes max when you have trained yourself and the patient and doing them.

Then we need to measure weight. Early weight gain is a big predictor of later weight gain. We also need to monitor at baseline three month, and then either annually or when there's more than seven percent of weight gain before that. We also need to monitor fasting blood work for glucose, triglycerides, total cholesterol, HDL and LDL cholesterol. When patients have a prolactin-raising medication, we might even want to measure prolactin because high levels can lead to sexual side effects, maybe bone density reduction, as well as potentially even breast cancer risk in longterm use. It's something that is basically our prerogative because if we prescribe these medications, we need to make sure that they're safe.

Christoph Correll, MD, is Professor of Psychiatry at The Zucker School of Medicine at Hofstra/Northwell, New York, USA, and Professor and Chair of the Department of Child and Adolescent Psychiatry, Charité University Medicine, Berlin, Germany. He is board certified in general psychiatry and child and adolescent psychiatry, having completed both residencies at The Zucker Hillside Hospital, NY. Since 1997, he has been working in New York, USA, and since 2017 he is also working in Germany again. Dr. Correll focuses on the early identification and treatment of youth and adults with severe mental illness, clinical trials, epidemiology, psychopharmacology, meta-analyses, and physical health in mental health. Since 2014, the beginning of this metric, he has been listed every year by Clarivate/Web of Science as one of the “most influential scientific minds” and “top 1% cited scientists in the area of psychiatry.”

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