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Tag: Antipsychotic induced weight gain

  • Metformin for Antipsychotic-Induced Weight Gain: What Took So Long?

    Metformin for Antipsychotic-Induced Weight Gain: What Took So Long?

    Antipsychotic-induced weight gain remains a significant challenge in psychiatric practice, contributing to metabolic syndrome, decreased quality of life, and reduced medication adherence. This issue is especially concerning given the chronic nature of psychiatric illnesses requiring antipsychotic treatment. Among strategies to address this, metformin—an insulin sensitizer primarily used for type 2 diabetes—has garnered considerable interest. Below, we summarize the evidence from randomized controlled trials (RCTs) evaluating metformin’s efficacy and safety in mitigating weight gain associated with antipsychotic medications.

    Evidence from Randomized Controlled Trials

    1. Meta-Analyses and Systematic Reviews
      • Multiple meta-analyses of RCTs have shown that metformin effectively reduces weight gain in individuals receiving antipsychotics. Weight reductions of 2-3 kg over 12-16 weeks have been reported compared to placebo.
      • Beyond weight loss, improvements in metabolic parameters such as fasting glucose, insulin resistance, and lipid profiles have been observed.
    2. Population-Specific Findings
      • First-Episode Psychosis (FEP): Studies indicate that metformin is particularly effective in individuals with FEP who experience rapid weight gain shortly after initiating antipsychotic therapy. Early intervention appears to yield more substantial benefits.
      • Chronic Schizophrenia: RCTs in populations with chronic schizophrenia have demonstrated similar weight-reducing effects, though results may be less pronounced compared to FEP patients.
    3. Adjunctive Lifestyle Interventions
      • Combining metformin with lifestyle interventions, such as diet and exercise counseling, results in synergistic benefits. RCTs demonstrate that this combination is more effective than metformin or lifestyle changes alone.

    Safety and Tolerability

    Metformin is generally well-tolerated. The most common side effects are gastrointestinal (e.g., nausea, diarrhea), which tend to subside with continued use. Rarely, lactic acidosis—a serious adverse event—can occur, particularly in individuals with renal impairment. It is crucial to monitor kidney function periodically.

    Practical Considerations

    1. Dosing: Initiate metformin at a low dose (e.g., 500 mg once daily) to minimize gastrointestinal side effects, and titrate gradually to a typical maintenance dose of 1,000-2,000 mg per day.
    2. Monitoring: Regularly assess weight, BMI, fasting glucose, and lipid profiles. Monitor renal function before and during treatment.
    3. Patient Selection: Metformin may be particularly beneficial for patients who:
      • Have significant weight gain or metabolic disturbances from antipsychotic use.
      • Are early in their antipsychotic treatment course.
      • Have no contraindications, such as severe renal impairment.

    Conclusion

    Metformin offers a promising strategy for mitigating antipsychotic-induced weight gain, supported by robust evidence from RCTs. While not a standalone solution, it can play a critical role in a comprehensive approach to managing the metabolic side effects of antipsychotics. Clinicians should consider metformin’s inclusion in treatment plans for patients struggling with weight gain or metabolic dysfunction related to antipsychotic treatment.

  • Rethinking Antipsychotics: Is It Time to Hit Pause for Schizophrenia Patients

    Rethinking Antipsychotics: Is It Time to Hit Pause for Schizophrenia Patients

    The article “Deprescribing Antipsychotics in Patients with Schizophrenia: Findings from a Specialized Clinic” emphasizes a growing interest in reducing or discontinuing antipsychotic medications in patients with schizophrenia, particularly those stable on long-term treatment. While continuous antipsychotic use is common to prevent relapse, concerns about long-term side effects, such as metabolic give us pause and rise concerns. 

    Key Points:

    1. Benefits of Deprescribing:
      • Reduction in side effects such as weight gain and metabolic syndrome.
      • Potential reversal of tardive dyskinesia.
      • Empowering patients by involving them in shared decision-making, improving adherence and satisfaction.
    2. Risks:
      • The primary risk is relapse, with studies indicating relapse rates between 20-60% after discontinuation.
      • Relapse can lead to hospitalization, job loss, and disrupted relationships.
    3. Strategies for Safe Deprescribing:
      • Individualized Tapering: Gradual reduction in dose is essential, tailored to the patient’s specific needs and history.
      • Relapse Prevention: Engaging support systems (family, mental health teams), monitoring for early signs of relapse, and incorporating psychosocial interventions.
      • Ethical Considerations: Balancing patient autonomy with the duty to minimize harm is a challenge. Encouraging patient participation respects autonomy while ensuring they are aware of risks.

    Future Directions:

    • More research is needed on long-term outcomes of deprescribing, particularly in identifying which patients are the best candidates for safe withdrawal.
    • Clinical guidelines should better integrate recovery-oriented approaches with deprescribing efforts to strike a balance between risk mitigation and promoting patient empowerment​

    link to the article: https://www.cambridge.org/core/journals/psychological-medicine/article/deprescribing-antipsychotics-in-patients-with-schizophrenia-findings-from-a-specialized-clinic/DA2F622FFA9D26A1F119F4F9BC11F2E3

  • Boosting the Mind: How Antipsychotics Impact Cognitive Function

    Boosting the Mind: How Antipsychotics Impact Cognitive Function

    Antipsychotic Drugs and Cognitive Function: Key Findings from a Systematic Review and Meta-Analysis

    Background:
    Cognitive impairment is a core feature of schizophrenia, often leading to significant functional disability. Antipsychotic medications are the main treatment for schizophrenia, but their impact on cognitive function remains debated.

    Objective:
    This systematic review and network meta-analysis aimed to compare the effects of different antipsychotic drugs on cognitive function in patients with schizophrenia.

    Methods:
    The review included randomized controlled trials (RCTs) that assessed cognitive outcomes in patients with schizophrenia treated with antipsychotics. A network meta-analysis was conducted to compare the cognitive effects across different antipsychotic drugs.

    Key Findings:

    1. Cognitive Improvement:
      • All antipsychotics studied showed modest cognitive benefits, though the effect sizes were small.
      • Second-generation antipsychotics (SGAs) generally performed better than first-generation antipsychotics (FGAs).
      • Among SGAs, lurasidone and amisulpride demonstrated the most pronounced cognitive improvements.
      • FGAs like haloperidol showed the least benefit for cognitive function.
    2. Domains of Cognitive Improvement:
      • The drugs improved different cognitive domains, including working memory, processing speed, and executive functioning, though no single drug showed superiority across all domains.
    3. Comparative Effectiveness:
      • In head-to-head comparisons, lurasidone and amisulpride were consistently ranked higher for cognitive improvement.
      • Olanzapine and risperidone also showed beneficial effects, though to a lesser extent.
    4. Adverse Effects and Tolerability:
      • Cognitive improvements were often seen alongside side effects, with some drugs (e.g., olanzapine) associated with metabolic risks that may counterbalance cognitive benefits.
    5. Limitations:
      • The analysis emphasized the small effect sizes, suggesting that while antipsychotics may slightly improve cognition, the changes may not be clinically meaningful in many cases.
      • Cognitive rehabilitation therapies may need to be paired with pharmacological treatment for more significant cognitive gains.

    Conclusions: While antipsychotics can modestly improve cognitive function in schizophrenia, the benefits are relatively small, and no drug significantly outperforms others across all cognitive domains. Lurasidone and amisulpride may offer the greatest cognitive benefits, but additional interventions may be necessary to address cognitive deficits effectively.

  • Navigating First-Episode Psychosis: A Delicate Balance

    Navigating First-Episode Psychosis: A Delicate Balance

    In my practice, I encounter many cases of first-episode psychosis, a critical period that requires thoughtful and precise intervention. The decisions made during this time can set a patient on the path to long-term recovery or, unfortunately, towards a lifetime of challenges.

    There are a few guiding principles I always adhere to:

    1. Most antipsychotics can be effective, but it’s important to choose carefully.
    2. Lower doses often suffice to achieve remission in first-episode psychosis. Starting with a medication that has a lower risk of cardiometabolic side effects and weight gain is crucial, especially for young patients. They shouldn’t be burdened with long-term physical side effects as they navigate their recovery.

    Predicting whether a patient will experience a single episode or develop a chronic condition like schizophrenia is challenging. While family history and substance use, particularly cannabis, can provide clues, there is still uncertainty.

    I believe that after 6-12 months of treatment, it’s worth considering tapering the antipsychotic to the lowest effective dose, with a careful eye on any signs of relapse. Unfortunately, what I often see is that both patients and clinicians overlook the subtle signs of relapse because they’ve mutually decided to discontinue the medication. By the time I see them again, the situation has worsened.

    Early psychosis treatment requires a delicate balance between managing symptoms and minimizing long-term side effects, all while keeping a close watch for signs of relapse. Careful planning is key to setting patients on the best path forward.

  • Suicidal Signals with Semaglutide? Experts Say, Don’t Panic Yet!

    Suicidal Signals with Semaglutide? Experts Say, Don’t Panic Yet!

    I recently had a case involving a person with no prior history of mental illness who suddenly developed acute suicidal thoughts. The only recent change in their life was starting a glucagon-like peptide-1 (GLP-1) agonist for diabetes. They reported noticeable mood changes and even suspected the medication was the cause based on their own experience. While we can’t draw any definitive conclusions about causation at this point, it’s reasonable to advise people, especially those with a psychiatric history, to carefully monitor for mood changes and suicidal thoughts when starting this type of medication.

    https://www.medscape.com/viewarticle/signal-suicidality-glp-1-ra-semaglutide-experts-urge-caution-2024a1000fa7?ecd=wnl_peerpulse_pos1_240823_etid6769391&uac=267049CZ&impID=6769391 

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    The Neurobiology of Appetite

    Metabolic set point 

    People alter the quantity and frequency of food consumption daily and yet the brain seems to have a regulatory process that allows people to maintain a relatively stable body weight. 

    Isn’t that crazy? 

    Anyone who has ever tried to diet knows all too well about this metabolic set point. There are staggeringly low rates of success with diet programs. A systematic review of studies published between 1931 and 1999 found that only 15% of patients achieved dietary success after 5 years. Most people who diet will slowly return to their preexisting weight within 1 year.

    This metabolic set point appears to be controlled by our genetics. There is a strong correlation between the body mass of biological parents and adoptees in adoption-based studies. In the case of weight, genetics has far more influence than environmental factors. 

    Despite all this obesity rates in the United States as well as other developed countries continues to rise, so what gives? 

    Our genes have difficulty responding to the modern environment. 3000 years ago, when food sources were scarce, it was advantageous to consume and store as many calories as possible. However, in the modern world where there is no shortage of opportunity to consume calorie dense foods, our genetics are working against us. The weight issue is genetic but also influenced by availability of high-calorie delicious food. 

    When it comes to weight, energy in (food) must equal energy out (heat and work). The energy out is made up of the resting metabolic rate (calories burned when the body is stationary) and physical activity. The brain has a unique mechanism for managing the RMR. When more calories are consumed the RMR increases and when we diet the RMR is turned down. 

    To solidify the point, we can look no further than The Biggest Loser competition. Investigators assessed 14 of the 16 contestants before the competition, after completion of the 30-week program, and 6 years after the show. 13 of the 14 study participants regained weight and 4 were heavier than when they started the competition 6 years ago. The real downer was they all burned less calories at rest 6 years after the show ended. Despite exercising more and theoretically being much healthier their RMR decreased. 

    What are the important signals used by the body that indicate when to eat and when to stop eating?

    Short-Term signels include: 

    Glucose: This is the primary nutrient that mediates satiety. Hypoglycemia will stimulate hunger and increase eating, while glucose infusions will decrease food intake. 

    Mechanoreceptors in the gut: The physical presence of food in the stomach activates these receptors due to stretching, the vagus nerve transmits signals of gastric stretch to the hindbrain to decrease eating. 

    Gut Hormones: The most well understood is cholecystokinin (CCK) which is released by endocrine cells in the small intestine. This will inhibit further food intake by stimulating the vagus nerve and decreasing gastric emptying. People have tried using CCK as a weight loss measure but all it does is decrease the size of meals but increases the frequency of eating thus producing a net zero effect on weight loss.

    Ghrelin is the only gut hormone that stimulates hunger. Some suggest that decreased ghrelin produced by the stomach is the reason gastric bypass surgery is effective for weight loss. 

    It’s now known that adipose tissue releases a hormone that conveys information about energy stores. Leptin is produced by fat cells and increases or decreases based on the total amount of fat. Leptin is a hormone that tells the body to stop eating. In the case of obesity leptin levels are high and energy expenditure increases while food intake decreases. When someone goes on a diet and fat stores decrease leptin decreases resulting in decreased energy expenditure and increased food intake. 

    Two groups of neurons in the arcuate nucleus of the hypothalamus mediate the leptin signal, proopiomelanocortin (POMC) and neuropeptide Y (NPY). POMC stops eating and NPY increases food intake and decreases energy expenditure. In obesity there is increased leptin which inhibits NPY and activates POMC resulting in increased energy expenditure and decreased food intake. The opposite is true for the lean individual. 

    Eating and Pleasure

    It’s well established that eating can result in pleasure, we have all had this experience after a stressful week a good meal can instantly change our mindset. The pleasure from food is likely an adaptation that enhanced survival when food sources were scarce. Increased dopamine in the nucleus accumbens and release of endogenous opioids appears to be more active when we are eating a meal we enjoy.