Does Abilify cause weight gain? Explore the scientific reasons behind aripiprazole-induced weight gain, including appetite changes, metabolic effects, and interactions with other medications. Discover strategies to mitigate weight gain while taking this antipsychotic medication.

Aripiprazole and Its Impact on Weight

Aripiprazole, commonly known as Abilify, is an atypical antipsychotic medication used to treat various mental health conditions, including schizophrenia, bipolar disorder, and depression. While it has been found to cause less weight gain compared to other antipsychotics, there is still evidence that aripiprazole can lead to significant weight gain in certain individuals, particularly when combined with certain antidepressants.

Factors Contributing to Aripiprazole-Induced Weight Gain

There are several mechanisms by which aripiprazole can contribute to weight gain, and the specific factors may vary from person to person.

1. Increased Appetite and Cravings

Some individuals report an insatiable appetite or frequent cravings, especially for carbohydrates and sugary foods, when taking aripiprazole. This increased appetite can lead to higher caloric intake and subsequent weight gain.

2. Blood Sugar Regulation Disruption

Aripiprazole has been associated with high blood glucose levels in some people, which can contribute to weight gain. However, the impact on blood sugar regulation is not consistent across all studies, and the risk of developing diabetes appears to be relatively low.

3. Metabolic Rate Changes

Aripiprazole may affect the brain’s regulation of metabolism, including the hypothalamus, which is crucial for maintaining a healthy metabolic rate. This disruption can slow down metabolism, leading to weight gain even without significant changes in diet or exercise habits.

4. Sedation and Reduced Physical Activity

Aripiprazole can cause tiredness and drowsiness, which may make it challenging for some individuals to maintain regular exercise routines. This reduction in physical activity can contribute to weight gain.

5. Interactions with Other Medications

When aripiprazole is combined with certain antidepressants, such as those with high activity at serotonin receptors, the interaction can lead to an increased risk of weight gain. However, this effect is less pronounced when aripiprazole is combined with low-serotonergic antidepressants.

6. Mood Improvement and Increased Social Engagement

As aripiprazole can improve mood, some individuals may feel more inclined to socialize and engage in activities that involve dining out or consuming high-calorie foods, potentially leading to weight gain.

7. Genetic Susceptibility

Variations in the gene that codes for the 5-HT2C receptor have been linked to an increased susceptibility to weight gain with atypical antipsychotics, including aripiprazole.

Strategies to Mitigate Aripiprazole-Induced Weight Gain

To address the issue of weight gain associated with aripiprazole, a multifaceted approach is often recommended, including the following strategies:

Monitoring and Early Intervention

Regularly monitoring weight and being vigilant for signs of weight gain can help identify the issue early, allowing for prompt intervention and adjustments to the treatment plan.

Dietary and Lifestyle Modifications

Adopting a healthy, balanced diet and engaging in regular physical activity can help mitigate the weight gain associated with aripiprazole. Providing education and support for these lifestyle changes is crucial.

Medication Adjustments

In some cases, changing the dosage or switching to a different antipsychotic medication with a lower risk of weight gain may be necessary to manage the issue effectively.

Combination Therapy

Combining aripiprazole with medications that have a weight-neutral or weight-reducing effect, such as certain antidepressants or medications that target specific metabolic pathways, may help counteract the weight gain associated with aripiprazole.

Importance of Individualized Approach

The impact of aripiprazole on weight can vary significantly among individuals, and a personalized approach to managing this side effect is essential. Healthcare providers should work closely with patients to identify the contributing factors, implement tailored interventions, and closely monitor progress to ensure the optimal management of aripiprazole-induced weight gain.

Conclusion

While aripiprazole is generally associated with a lower risk of weight gain compared to other antipsychotics, it can still lead to significant weight gain in some individuals. Understanding the various mechanisms underlying this side effect and implementing appropriate mitigation strategies is crucial for ensuring the safe and effective use of aripiprazole in the management of mental health conditions.

Does Abilify cause weight gain?

Medically reviewed by Carmen Pope, BPharm. Last updated on July 19, 2022.

Although Abilify (aripiprazole) has been found to cause less weight gain than other atypical antipsychotics, there is evidence that in certain people it can cause significant weight gain and it may be more likely to cause weight gain in people who are taking it for depression alongside other antidepressants. Side effects such as weight gain may be significant enough for some people to discontinue Abilify, even when it is working well to manage symptoms.

Why does Abilify cause weight gain?

Abilify is likely to cause weight gain in several different ways. If you are someone who has gained weight with Abilify, the way you have gained weight may be different from someone else, for example, you may have noticed that your appetite has increased whereas somebody else may still be eating the same diet but feel that their metabolism has slowed. In most cases, a combination of factors is probably to blame for your weight gain.

Here are some ways Abilify causes you to gain weight:

1. Abilify may increase your appetite or cravings

Some people report on Blog sites that they develop an insatiable appetite with Abilify or are always feeling extremely hungry. No matter what they eat, they never feel satisfied and end up craving something else, usually carbohydrates or sugar. For some, the appetite increase is slight, for others it is significant. Increasing how much food you eat each day will cause you to gain weight.

2. Abilify may affect your blood sugar levels

Postmarketing reports have shown that Abilify (aripiprazole) is associated with high blood glucose (sugar) levels in some people, but this is not consistent and many studies report Abilify (aripiprazole) has a low potential to affect blood glucose levels and cause diabetes. Four case studies reported diabetic ketoacidosis with aripiprazole use: a 44-year-old man who developed DKA within 2 weeks of aripiprazole initiation; a 12-year-old boy who developed DKA within 6 months of initiation; a 34-year-old female who developed DKA within 4 days of administration; and a 33-year-old male who developed DKA within 18 months of aripiprazole initiation. All instances were resolved with aripiprazole discontinuation and appropriate management.

Big spikes in blood glucose levels followed by large drops can cause tiredness and hunger.

3. Abilify may affect your metabolism

Our brain, especially our hypothalamus, is crucial to regulating metabolism. The hypothalamus takes information from nerve cells outside of the brain, hormones, other chemicals, such leptin and ghrelin, nutrients, such as glucose, amino acids, and fatty acids, as well as effects on neurotransmitter receptors, such as 5-HT2C and 5-HT1A receptors, histamine h2 receptors and dopamine D2 receptors to regulate metabolism. Abilify affects some of these receptors more than others, which may slow down metabolism, resulting in weight gain even when dietary and exercise habits have not changed.

4. Side effects may make you less likely to exercise and more likely to eat

Abilify can cause tiredness and drowsiness that may make it difficult for you to stay motivated, get out of bed, or do exercise. If you are unable to do regular exercise this may also slow your metabolism.

5. Abilify may be more likely to cause weight gain when combined with certain other medications

Serotonin (5-HT)2C receptors play an important role in helping to regulate our moods, our activity levels, and our appetite, in addition to some other functions. One review found that when aripiprazole was combined with antidepressants that had high activity at serotonin receptors (such as citalopram, fluoxetine, paroxetine, sertraline, or venlafaxine), it acted as an antagonist at the receptor which resulted in weight gain. But when it was combined with a low serotonergic antidepressant, such as bupropion, there was little or no weight gain.

The authors concluded that this might explain why aripiprazole was found to have a low weight gain potential in studies focusing on schizophrenia and bipolar disorder that had minimal use of antidepressants.

6. Abilify can improve your mood which may make you more likely to go out to eat

Many people start Abilify because their mood is low or they have trouble controlling their thoughts. Once you start to feel better you may feel like socializing and going out more which usually involves dining out or getting fast food.

7. Your genetics may make you more susceptible to weight gain

Some people are just more likely to gain weight than others. Variations in the gene that codes for the 5-HT2C receptor have been linked to a susceptibility to gain weight with atypical antipsychotics. This may explain why there is a wide variation in how much weight people gain (or lose) while taking Abilify. One day there may be a blood test to identify people who are more at risk of gaining weight or other side effects, but currently, there is not one available.

How much weight will I gain with Abilify?

How much weight you end up gaining with Abilify depends on the dose you take, the length of time you take it, what other medications you may be on and what you weigh before you started taking Abilify. Weight gains of 2.2 lb (1kg) to 90lb (40kg) have been reported and weight gains are more likely the higher dosage of Abilify you take if you also take antidepressants such as citalopram or venlafaxine and if you were of normal weight or even underweight to start with. Some people who take Abilify may also experience weight loss.

People who were normal or slightly underweight before starting aripiprazole were more likely to gain weight as reported in a large RCT that included 155 people with aripiprazole; the average weight gain was 2.7kg after 52 weeks. People who were overweight or obese gained an average of 0.7kg and 0.1kg respectively and across the total sample, an average of 1kg was gained.

An analysis of 13 placebo-controlled trials of people with schizophrenia or bipolar disorder showed an average weight loss of 1.5kg in those trials using aripiprazole as monotherapy and an average weight gain of 1.7kg after 14 weeks when aripiprazole was added to ongoing antidepressant treatment.

Children and adolescents found an average increase in body weight of 1.6kg after 42 to 43 days, which increased to 5.8kg after 24 weeks. Another trial in adolescents reported that 32.8% of patients gained at least 7% of their body weight after 26 weeks.

How can I prevent weight gain with Abilify?

Talk to your doctor if you have gained significant weight while taking Abilify about ways to help lose weight which may include:

• Watch your portion size, eat regular meals, and cut down on foods high in sugar and fat
• Weigh yourself every day so you can keep on top of small weight increases
• Exercise daily for at least 1 to 2 hours
• Reducing the dose of Abilify
• Switching Abilify for a different medication
• If you take an antidepressant with Abilify then maybe switch to a different antidepressant, such as bupropion, which has less effect on serotonin receptors
• Adding low-dose Topamax (topiramate) to Abilify treatment as a weight-reducing treatment.

Will I lose weight after stopping Abilify?

Most people do lose weight after stopping Abilify; however, it may depend on how long you have been overweight, and what new medication you are put on. To lose weight, you will still have to follow a heart-healthy diet and exercise every day.

Are there any alternative drugs that do not cause weight gain?

There are usually alternative medications you can take instead of Abilify if you have gained weight while taking Abilify. The choice of medication depends on your condition and what other medications you already take. Talk to your doctor about alternatives to Abilify.

References

• Abilify (aripiprazole). Updated 08/2021. Otsuka America Pharmaceutical, Inc. https://www.drugs.com/pro/abilify.html
• Mental Health Daily. (2015). Abilify and Weight Gain: Causes & Contributing Factors. https://mentalhealthdaily.com/2015/01/29/abilify-and-weight-gain-causes-contributing-factors/
• Nguyen, C. T., Rosen, J. A., & Bota, R. G. (2012). Aripiprazole partial agonism at 5-HT2C: a comparison of weight gain associated with aripiprazole adjunctive to antidepressants with high versus low serotonergic activities. The primary care companion for CNS disorders, 14(5), PCC.12m01386. https://doi.org/10.4088/PCC.12m01386
• Singh T. (2005). Aripiprazole-induced weight gain. Psychiatry (Edgmont (Pa. : Township)), 2(6), 19.
• Dayabandara, M., Hanwella, R., Ratnatunga, S., Seneviratne, S., Suraweera, C., & de Silva, V. A. (2017). Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatric disease and treatment, 13, 2231–2241. https://doi.org/10.2147/NDT.S113099
• Psych Scene Hub. (2022). Antipsychotic Induced Weight Gain and Metabolic Dysfunction – A Review of Pathophysiology and Management Strategies. https://psychscenehub.com/psychinsights/antipsychotic-weight-gain-metabolic/
• Makhzoumi, Z. H., McLean, L. P., Lee, J. H., & Ibe, A. I. (2008). Diabetic ketoacidosis associated with aripiprazole. Pharmacotherapy, 28(9), 1198–1202. https://doi.org/10.1592/phco.28.9.1198
• Radhika D., & Rajanshu V. (2008).Diabetic Ketoacidosis Induced by Aripiprazole in a 12-Year-Old Boy. Diabetes Care, 31 (6), e50. https://doi.org/10.2337/dc08-0441
• Holt R. (2019). Association Between Antipsychotic Medication Use and Diabetes. Current diabetes reports, 19(10), 96. https://doi.org/10.1007/s11892-019-1220-8
• Church, C. O., Stevens, D. L., & Fugate, S. E. (2005). Diabetic ketoacidosis associated with aripiprazole. Diabetic medicine: a journal of the British Diabetic Association, 22(10), 1440–1443. https://doi.org/10.1111/j.1464-5491.2005.01628.x
• Reddymasu, S., Bahta, E., Levine, S., Manas, K., & Slay, L. E. (2006). Elevated lipase and diabetic ketoacidosis associated with aripiprazole. JOP: Journal of the pancreas, 7(3), 303–305.
• McIntyre, R. S., McElroy, S. L., Eudicone, J. M., Forbes, R. A., Carlson, B. X., & Baker, R. A. (2011). A 52-week, double-blind evaluation of the metabolic effects of aripiprazole and lithium in bipolar I disorder. The primary care companion for CNS disorders, 13(6), PCC.11m01182. https://doi.org/10.4088/PCC.11m01182
• Shivakumar, V., Jayaram, N., Rao, N. P., & Venkatasubramanian, G. (2012). Successful use of add-on topiramate for antipsychotic-induced weight gain. Indian journal of psychological medicine, 34(1), 85–86. https://doi.org/10.4103/0253-7176.96168

Related medical questions

• Does Abilify cause gambling addiction?
• Why should you take aripiprazole in the morning?
• Vraylar vs Abilify – How do they compare?
• What is the difference between Abilify and Abilify Maintena?
• How does Abilify MyCite work?
• How to sleep while taking Cymbalta?
• Can depression cause headaches?
• SSRI’s vs SNRI’s – What’s the difference between them?
• How long does Xanax last for / stay in your system?
• Klonopin vs Xanax – How are they different?
• Why does Lexapro cause weight gain?

Drug information

• Abilify
• Aripiprazole

Related support groups

• Abilify
  (144 questions, 660 members)
• Aripiprazole
  (21 questions, 44 members)
• Depression
  (2,089 questions, 8,656 members)
• Weight Loss (Obesity/Overweight)
  (700 questions, 1,433 members)
• Schizophrenia
  (87 questions, 316 members)
• Bipolar Disorder
  (470 questions, 3,134 members)
• Schizoaffective Disorder
  (53 questions, 238 members)

Medical Disclaimer

Abilify Side Effects | Compulsive Behavior & Withdrawal Symptoms

Common Abilify (aripiprazole) side effects include nausea, vomiting, headache, insomnia and weight gain. Serious Abilify side effects include tardive dyskinesia and neuroleptic malignant syndrome. Stopping Abilify may cause withdrawal. Abilify withdrawal symptoms include anxiety, panic attacks and sweating.

Common Abilify Side Effects

Common side effects of Abilify include nausea, vomiting, dizziness, anxiety, insomnia, constipation, movement disorders and restlessness. The most common side effect is headaches.

Abilify, also known as aripiprazole, is an atypical antipsychotic medication that doctors prescribe for major depressive disorder, bipolar I disorder and schizophrenia, and to manage irritability from autism spectrum disorder or Tourette’s syndrome in children.

Other common side effects of Abilify include:

• Blurred vision
• 
  Drooling
• 
  Drops in blood pressure when standing up
• 
  Constipation
• 
  Choking or trouble swallowing

Sleepiness is a common Abilify side effect for children ages 6 to 18. Other side effects for children include headache, nausea, vomiting, insomnia, movement disorders, increased appetite and weight gain.

If the drug does not reduce psychiatric symptoms, consider asking your doctor to switch you to a different antipsychotic medication.

Serious Side Effects of Abilify

Abilify can cause serious side effects, many of which can be dangerous to long-term physical and mental health. These include seizures, involuntary muscle movements and neuroleptic malignant syndrome. The drug is also associated with harmful metabolic changes, including weight gain, increased cholesterol, low white blood cell counts, insulin resistance and nonalcoholic fatty liver disease.

Abilify can cause new and worsening suicidal thoughts and impulse control disorders. People experiencing impulse control while taking Abilify might engage in behaviors such as compulsive gambling, hypersexuality, compulsive shopping and spontaneous wandering. Recent reports suggest Abilify might also cause obsessive-compulsive thoughts and behaviors.

Black Box Warning for Elderly Dementia Patients

Abilify’s drug label includes a black box warning stating that elderly people with dementia who take the drug are at an increased risk of death. In clinical trials, elderly people with dementia taking atypical antipsychotics such as Abilify were 1.7 times more likely to die than those in the control group.

Clinical data does not spell out the reason for this increased mortality risk, but suggests the problem is caused by multiple factors. Elderly people who take antipsychotics such as Abilify are more likely to suffer strokes, which are often fatal within this population. They may also be more vulnerable to cardiovascular events such as heart attacks and serious infections such as pneumonia.

Doctors normally prescribe Abilify for elderly patients with dementia when there is a serious risk the person will harm themselves or others. In some cases, the risks are necessary to prevent greater harm. If you or a loved one with dementia have a prescription for Abilify, take it exactly as directed by your doctor.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome is a rare, life-threatening reaction to antipsychotic drugs such as Abilify. It is a potential side effect of almost all antipsychotic drugs.

Characteristics of NMS include fever, altered mental status, muscle rigidity and instability of the autonomic nervous system. This system controls unconscious functions such as breathing, heart rate, digestion, urination and sexual arousal.

Tardive Dyskinesia (Uncontrolled Body Movements)

Tardive dyskinesia, another serious side effect of Abilify, is characterized by involuntary muscle movements throughout the body, but mostly in the lower face.

TD is most common among people who take Abilify for months or years, but it can manifest as soon as six weeks after beginning the drug. TD can go away after you stop taking Abilify, but sometimes it becomes a permanent condition.

Abilify and Weight Gain

Studies also link Abilify to weight gain, particularly in children. A 2022 review in Australasian Psychiatry examined 11 studies and found that young people (mean age 18) gained an average of 2.7 kg (6 pounds) while on aripiprazole. Youths who took the drug for longer periods (more than 12 weeks) gained more weight than those who took it for shorter periods. Dosage sizes had no impact on weight gain.

Abilify sometimes causes weight gain in adults. This happens less often than it does in children, and the total weight gain is usually less significant. Studies suggest that aripiprazole is less likely to cause weight gain in adults than most other antipsychotics in use today.

Abilify Withdrawal

Because Abilify affects how your brain works, stopping the drug all at once may lead to withdrawal symptoms. This is more likely when you quit the drug after long-term use or if you are used to taking high doses of the medication.

Abilify withdrawal symptoms include:

• Anxiety
• 
  Appetite changes
• 
  Concentration problems
• 
  Confusion
• 
  Depression
• 
  Diarrhea
• 
  Dizziness
• 
  Hallucinations
• 
  Headache
• 
  Joint pain
• 
  Panic attacks
• 
  Sweating
• 
  Vomiting

Experts recommend tapering off Abilify if you want to stop taking it. Always consult your doctor for correct dosages when weaning yourself off of the drug.

Impulse Control Issues from Abilify

In 2014, a study published in JAMA Internal Medicine found that dopamine receptor agonist drugs such as Abilify were associated with new and worsening impulse control disorders. This research led to a new warning on the drug’s label, mandated by the U.S. Food and Drug Administration. This warning cautions that the drug may cause serious impulse control problems such as problem gambling, compulsive shopping and binge eating.

A 2022 review of impulse control disorder reports uploaded to the FDA Adverse Event Reporting System since December 2020 confirms that this association is still ongoing. About 94% of the impulse control disorder reports examined during the study involved people taking aripiprazole.

Many people who feel their lives were irreparably altered from gambling or uncontrolled impulse spending after taking the drug filed Abilify lawsuits to seek compensation.

Impulse control problems related to Abilify often go away when you stop taking the drug or reduce your dose. If you struggle with impulse control, talk to your doctor about reducing the dose or switching medications. Don’t lower your dosage or stop taking your medication without informing your doctor.

Compulsive Gambling

Problem gambling is the most common impulse control-related side effect of Abilify. The medication may be more likely to cause gambling problems than other related drugs with similar impulse control effects. A 2021 study of Swedish health records found that people taking Abilify were significantly more likely to develop problem gambling behaviors than people taking other dopamine agonists.

Most of those who develop gambling issues while taking Abilify have no prior history of problem gambling. Contact your doctor immediately if you have the urge to gamble more frequently than usual.

Sexual Side Effects of Abilify

Hypersexuality is another manifestation of Abilify’s effects on impulse control. This includes having unprotected sex, compulsive masturbation, having sex with multiple partners, or having sex outside of a committed relationship. Some people engage in sexting or share explicit images of themselves.

FDA data shows that 34% of people affected by antipsychotic-related impulse control disorders display uncharacteristic hypersexual thoughts or behaviors. Like Abilify’s other impulse control side effects, hypersexual behavior usually stops when you stop taking the drug or lower your dose.

Suicidal Thoughts

People who take Abilify have an increased risk of developing suicidal thoughts and behaviors. For those who already experience these issues, Abilify may worsen them. The drugmaker now notes this side effect in the black box warning on the drug’s label.

Monitor yourself for new or worsening suicidal thoughts while taking Abilify. Contact your doctor immediately if you notice them. Don’t stop taking your medication without your doctor’s knowledge.

Aripiprazole Side Effects

Please seek the advice of a medical professional before making health care decisions.

•  
•  
•  

TELL US WHAT YOU THINK

Did You Find Drugwatch Helpful?

Yes

No

Thank you for your feedback. Do you have any thoughts you’d like to share about Drugwatch.com?

This article changed my life!

This article was informative

I have a question

How can we improve this page?

This article contains incorrect information

This article doesn’t have the information I’m looking for

I have a question

How can we improve this page?

Thank You for Your Feedback

We appreciate your feedback. One of our content team members will be in touch with you soon.

We appreciate your feedback. One of our content team members will be in touch with you soon.

✚ Weight gain while taking antipsychotics. Neuropsychiatric clinic of Professor Minutko. Article #7004

Many factors contribute to weight gain in patients with psychiatric disorders, particularly psychosis. A sedentary lifestyle, unhealthy eating habits, genetic susceptibility and antipsychotics are considered to be the main contributing factors here to weight gain. Unfortunately, only one third to one half of patients adequately control the metabolic side effects of antipsychotics.

In addition to weight gain, antipsychotics also affect glucose metabolism, increase cholesterol and triglyceride levels, and cause arterial hypertension, leading to metabolic syndrome. Metabolic syndrome increases the risk of developing diabetes by five times and cardiovascular disease by two times over the next 5-10 years after the diagnosis of this syndrome. The prevalence of metabolic syndrome is high in schizophrenia. A meta-analysis of 77 publications showed an overall prevalence of this syndrome in schizophrenia of 32.5%. A similar meta-analysis performed in patients with first episode schizophrenia found lower rates of metabolic syndrome (~10%). In other words, during treatment with antipsychotics, the number of overweight patients increases by almost 3 times. However, the level of obesity in the first psychotic episode remains high – 22%.

Weight gain caused by antipsychotics is one of the main problems in the treatment of patients with mental disorders. Most antipsychotics cause weight gain, with olanzapine and clozapine appearing to be at the highest risk of this side effect.

Dynamics

Weight increases rapidly during the initial period of therapy with these drugs, almost immediately after the start of antipsychotics. In the future, patients also continue to gain weight. In the first few weeks after starting antipsychotic medication, there is a rapid weight gain. The rate of weight gain then gradually decreases and levels off over several months.

Time to plateau varied for each antipsychotic, ranging from 4 to 9 months for olanzapine and 42 to 46 months for clozapine. This indicates that patients will continue to gain weight for 1–4 years. taking antipsychotics.

Factors associated with rapid initial weight gain were younger age, lower basal body mass index (BMI), greater response to antipsychotics, and increased appetite. Rapid weight gain of more than 5% in the first month is the best predictor of significant weight gain in the long term.

Complications

Researchers have shown that weight gain and obesity also lead to increased cardiovascular and cerebrovascular disease, reduced quality of life, and poor medication adherence.

Age-related aspects of weight gain with antipsychotics

Unlike adults, children are physically and emotionally more vulnerable to the side effects of medications.

Children are especially vulnerable to antipsychotic-induced weight gain. Atypical antipsychotics (SGA) are effective for psychiatric disorders in children, but their benefits are limited by the risks of both metabolic and neurological side effects. Weight gain is one of the most annoying side effects in children, with up to 80% of children showing significant weight gain. Adolescents experienced greater weight gain than older patients. Patients with autism treated with antipsychotics had greater weight gain. A higher propensity to gain weight is also observed in patients with schizophrenia.

Antipsychotic weight comparison

Clozapine, olanzapine, thioridazine, sertindole, chlorpromazine, and risperidone have been reported in the literature to cause significant weight gain ranging from 4.45 to 2.10 kg. Also note that all antipsychotics except haloperidol, lurasidone, and ziprasidone cause weight gain. Olanzapine and zotepine cause significantly more weight gain than most other antipsychotics. Another meta-analysis found that olanzapine and clozapine caused the greatest weight gain, while quetiapine, risperidone, and sertindole produced intermediate effects on weight. Moderate to low weight gain was observed with aripiprazole and amisulpiride. Newer antipsychotics, asenapine, iloperidone, paliperidone, and lurasidone, are reported to cause significant weight gain. Clinically significant weight gain greater than 7% was caused by all drugs except lurasidone. It is worth reminding the reader of my Blog that clozapine, the drug with the highest risk of weight gain, is also the only antipsychotic currently licensed for the treatment of resistant schizophrenia. Similarly, olanzapine, which ranks high in terms of efficacy, carries a higher risk of weight gain than most other antipsychotics.

Etiology

Genetics

Genetic polymorphisms may explain individual differences in AIWG. A recent meta-analysis by Zhang et al. (2016) , Identified 13 single nucleotide polymorphisms from nine genes significantly associated with AIWG. Single nucleotide polymorphisms associated with genes ADRA2A , DRD2 , 5- HTR2C and MC4R, showed the largest effect size, indicating that Candidate genes for weight gain also bind to receptors, via which antipsychotics exert their therapeutic effects.

Pathogenesis

Receptors

The amount of weight gain depends on the type of antipsychotic and the individual patient. The high likelihood of weight gain when taking antipsychotics is associated with their actions on serotonin 5-HT2A and 5-HT2C, dopamine D2 and D3, histamine h2, and muscarinic M3 receptors. The different effects on weight are explained by the different affinities of the drugs for these receptors.

Hormones

Antipsychotics affect neuropeptides associated with appetite control and energy metabolism. Leptin and adiponectin are adipokines produced in white adipose tissue that are involved in the pathogenesis of antipsychotic weight gain (AIWG). Elevated leptin levels and decreased adiponectin levels have been demonstrated with short-term and long-term treatment with olanzapine. Ghrelin, which acts on the hypothalamic arcuate nucleus to enhance food intake and store adipose tissue, is also affected by antipsychotics. Changes in leptin, adiponectin, and ghrelin levels are hypothesized to be related to direct drug exposure and not secondary to weight gain.

On the other hand, the effects of antipsychotics on lipid and glucose metabolism have been linked to their effects on weight gain and obesity, leading to insulin resistance and consequently increased release of triglycerides and very-low-density lipoproteins from adipocytes.

There is also evidence that antipsychotic drugs increase gene expression of the sterol regulatory element binding protein ( SREBP ) and very low density lipoprotein ( VLDL ).

Therapy

Personal selection of antipsychotic drugs according to the individual characteristics of the patient and careful monitoring of weight and other parameters (indicators) of metabolism are the best prevention of weight gain. Switching therapy to a drug with a lower propensity to cause weight gain is an option but carries the risk of a relapse of the psychiatric disorder. Non-drug therapies, such as regular nutritional consultations, specific exercise programs, cognitive training, and behavior change strategies, are equally effective in both individual and group work with patients.

Metformin is one of the drugs that is used for weight loss, however, in my opinion, it should be prescribed for elevated levels of glycated hemoglobin. Metformin has the most evidence of efficacy, while topiramate and reboxetine may also be effective. These drugs prevent or treat weight gain through various mechanisms. For example, metformin and rosiglitazone improve insulin resistance, while aripiprazole and metformin lower lipid levels.

Metformin is an antihyperglycemic agent that has been used for many decades. It exerts its action by inhibiting hepatic gluconeogenesis and improving insulin sensitivity in skeletal muscle via adenosine monophosphate kinase. It also lowers low-density lipoprotein cholesterol and triglycerides. The main mechanism of weight loss here may be the reduction of insulin resistance and appetite suppression. The data show that metformin leads to clinically significant weight loss in about half of patients.

The antiepileptic drug topiramate has shown promising results in the treatment of AIWG. Topiramate exerts its weight loss action by stimulating lipoprotein lipase while inhibiting carbonic anhydrase and lipogenesis. It also suppresses appetite and increases satiety. Low baseline levels of thyrotropin hormones predicted the amount of weight gained, and topiramate was particularly effective in reducing weight gain in this subgroup. Use of topiramate 100 or 200 mg showed a dose-response relationship for weight loss. There is evidence that topiramate may have a therapeutic effect on psychotic states, which may be explained by the antagonism of glutamate-induced excitotoxicity at α-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) and kainate receptors.

Norepinephrine reuptake inhibitors (NRIs), such as reboxitin, act by inhibiting the reuptake of norepinephrine. They are prescribed in order to reduce appetite, thereby causing weight loss. The study of atomoxetine did not give positive results. The cardiovascular side effects of changes in blood pressure and heart rate caused by NRIs may interfere with the weight loss benefits of this group of drugs. The combination of reboxetine-betahistine showed clinically significant attenuation of olanzapine-induced weight gain. Betahistine is a histaminergic H1 receptor agonist and H3 antagonist that has been investigated as a co-treatment for olanzapine-induced weight gain. The weight loss potential of betahistine is due to its action on the hypothalamus and liver to induce thermogenesis and reduce food intake. An additional benefit of taking this drug is the reduction in Epworth sleepiness scores during treatment.

The exact mechanism of action of the new antiepileptic drug zonisamide is unknown. It may act by changing the threshold for rapid inactivation of sodium channels in a voltage dependent manner. It also reduces persistent high-frequency action potential re-firing and inhibits low-threshold T-type calcium channels in neurons. Researchers have demonstrated that zonisamide leads to a moderate but persistent reduction in AIWG.

GLP-1 is an intestinal hormone synthesized in the intestinal mucosa. GLP-1 stimulates glucose-induced insulin secretion in the pancreas and inhibits glucagon secretion. In addition, it reduces appetite and food intake by activating central and peripheral GLP-1 receptors. A meta-analysis showed that GLP-1 reduced weight in obese, diabetic and non-diabetic patients compared to other antidiabetic drugs, including metformin.

Diethylpropion and phentermine are dopamine agonists that stimulate dopamine secretion. They are postulated to increase energy expenditure, resulting in weight loss. Both of these drugs are indicated for the short-term treatment of obesity. However, these two drugs have not been studied for AIWG.

Amantadine increases dopamine synthesis and release with some dopamine reuptake inhibition. It is also N – methyl – d – α-aspartate receptor antagonist. One study showed that amantadine 100–300 mg was effective in attenuating or inducing weight loss in patients who experienced weight gain with olanzapine.

H2 receptor antagonists such as famotidine and nizatidine are thought to reduce weight by suppressing appetite caused by increased cholecystokinin levels. An open study showed that treatment with nizatidine resulted in significant weight loss, and this correlated with leptin levels.

The glucocorticoid and progesterone antagonist mifepristone is effective in reducing weight gain in patients receiving risperidone or olanzapine. Modafinil exerts its action by stimulating monoaminergic receptors. One RCT showed that modafinil resulted in significantly less weight gain compared to placebo in patients treated with olanzapine. Although orlistat is FDA approved for weight loss, there is no evidence that it is effective against AIWG.

Non-drug strategies include cognitive and behavioral psychotherapy, diathetic counseling, and exercise. Cognitive strategies include understanding eating behavior and physical well-being. Behavior modification includes training in problem solving, proper goal setting, social support, and monitoring exercise and eating habits. Dietary counseling includes a reduction of 500–1000 kcal/day from the current diet and a reduction in dietary fat intake by up to 30% of energy intake. Exercise includes 150 minutes of moderate (55-69% of maximum heart rate) of exercise per week.

Treatment regimen

Just as extrapyramidal side effects lead to poor compliance (FGA), weight gain is a cause of non-adherence to SGA treatment. However, there is little direct evidence linking weight gain to poor adherence. Obese patients are 13 times more likely to stop taking medication due to weight gain than non-obese patients. This was also reported in the CATIE study, where more patients discontinued olanzapine due to weight gain compared to other drugs, despite olanzapine showing the lowest overall withdrawal rate.

On the other hand, it has also been noted that weight gain is indicative of a better response to antipsychotics, and as a result improved compliance can be expected. A recent study examining factors associated with poor adherence in patients with bipolar disorder reported no difference in adherence between different patient groups.

Quality of life

Weight gain affects patients’ quality of life and self-esteem. Waist circumference and body mass index (BMI) predict poor health-related quality of life in patients receiving antipsychotics. Weight gain, cognitive side effects, and sexual dysfunction are strongly associated with poor quality of life satisfaction and distress, especially in women. A change in self-identification follows a change in appearance as a result of weight gain.

There is evidence that patient weight gain is a concern for caregivers. A mail-order survey of relatives of patients with schizophrenia found that relatives rated weight as the second most problematic side effect. The biggest concern was drowsiness and sedation.

Researchers believe that adherence to treatment is determined by patients’ assessment of the benefits of treatment (including side effects) and the risk of relapse, as well as the cost of treatment.

Blog Post Category:

Biological Psychiatry

You must enable JavaScript to use this form.

Your name *

Your phone number (privacy guaranteed) *

Main complaint *

Presumptive diagnosis

Taking medication

Email

Consent to the processing of personal data *

I agree to the processing of personal data, I have read the privacy policy

Second-generation antipsychotics cause rapid weight gain in children and adolescents

Incomplete draft translation in 2 hours. There may be blunders and the like.

Translation of Children and Teens Gain Weight Quickly on Second-generation Antipsychotics from the Schizophrenia Research Forum.

Second-generation antipsychotics cause rapid weight gain in children and adolescentsyears, roughly equal to 11 weeks from the start of treatment with second-generation antipsychotics, the weight of children and adolescents is increasing at an alarming rate. Researcher Christoph Korel of the Zucker Hillside Hospital in Glen Oaks, New York, and colleagues are also looking at links between some of these drugs and metabolic abnormalities that can later reward young patients with heart disease. The results of their study, as well as data from the recent TEOSS study (Therapy of Early Schizophrenia Spectrum Disorders), argue against the rampant use of these drugs in the treatment of various psychiatric disorders in young people.

The perceived superiority of second-generation drugs over pre-existing antipsychotics puts them at the forefront in the treatment of schizophrenia. However, recent data from studies in a cohort of adult patients suggest that most second-generation drugs, also called “atypical antipsychotics”, are not superior in effectiveness to their older, “typical” counterparts (see related news on the SRF website; news on SRF ; one more news on a similar topic on SRF).

Results from the TEOSS trial, one of the few randomized controlled comparisons of drugs used in early schizophrenia and schizoaffective disorder, published last year, showed that risperidone and olanzapine, two second-generation drugs, were no more successful in controlling symptoms than the first-generation molindone. (see Sikich et al., 2008; Frazier et al., 2007; McClellan et al., 2007). Weight gain from both second generation products was higher than from molindone. In particular, patients taking olanzapine gained 6.1 kg in just eight weeks, prompting the study’s Safety Review Board to stop enrolling volunteers in this referral. Olanzapine also increased insulin and lipid levels.

Starting with a clean slate

In contrast to the TEOSS study, Correll et al’s work was to study only those patients who were not yet taking or were taking few antipsychotics. In an interview given to the SRF website, Correll said that this cohort of patients came into their focus almost by accident. When studying weight gain in children and adolescents taking antipsychotics, they realized that those patients who had never taken antipsychotics prior to the study began to gain more weight. Then the researchers decided to focus only on those patients whose experience of taking drugs did not exceed one week.

The range of ages among 272 study subjects ranged from 4 to 19 years. The authors included 82 patients with schizophrenia spectrum disorders, 130 with mood disorders, and 60 with social behavior disorders (?disruptive behavior) or manifestations of aggression in behavior (?aggressive behavior spectrum). All of them received second-generation antipsychotics.

Rejecting random drug prescribing, Correll and colleagues asked clinicians who manage patients to choose their own drugs. The authors chose this approach in order to bring the overall picture closer to the real situation. As a consequence, the cohort included patients taking other drugs, although the authors excluded those taking more than one from the study.

Ziprasidone was taken by an insufficient number of subjects. Thus, the analysis included 41 patients on aripiprazole, 45 on olanzapine, 36 on quetiapine, and 135 on risperidone. Another 15 patients either refused therapy or dropped out during the first four weeks, but still completed the entire testing cycle. They served as a comparative group.

Researchers compared weights and metabolic rates across groups using an intent-to-treat approach to statistical data processing. Weight gain among participants in the comparison group was zero or negligible. In contrast, treatment lasting an average of 11 weeks resulted in an average weight gain of 8.5 kg in patients treated with olanzapine (95% CI = 7.4-9.7 kg). Weight gain in the case of other second-generation drugs was in the range of 6. 1 (quetiapine) – 5.3 kg (risperidone) – 4.4 (aripiprazole). In fact, half of the drug-treated patients gained more than 7% of their body weight.

As one would expect, as the weight was put on, the patients got fatter and accumulated fat. Correl and colleagues write that “in general, between 10% and 36% of patients progressed to overweight or obese status during those 11 weeks.”

In addition, the study revealed metabolic abnormalities. In younger users of either olanzapine or quetiapine, significant increases in cholesterol, triglycerides, low-density lipoprotein cholesterol, and triglyceride/HDL-cholesterol ratios were noted. Investigators also noted impaired glucose metabolism in olanzapine users and elevated triglycerides in risperidone users. In contrast, in those treated with aripiprazole, as well as in the control group, metabolic parameters remained stable. At first glance, this makes aripiprazole the winner, but a recent meta-analysis found it to be less effective than olanzapine (see related news on the SRF website).

Findings of weight gain and metabolic disturbances in young people treated with second-generation antipsychotics are consistent with existing small study data (eg Sikich et al., 2008; Fraguas et al., 2008). The results predict an unhealthy outlook for many patients. “Cardiometabolic side effects such as age-inappropriate weight gain, obesity, hypertension, and lipid and glucose abnormalities are especially troublesome for the developing organism, as they are predictors of future obesity, metabolic syndrome, cardiovascular mortality, and neoplasms,” write Correl. and colleagues. First-generation agents are also associated with an increased risk to the heart (see the news on the SRF website).

Warning bell

In an editorial in the same issue of JAMA in which the study appeared, Christopher Varley and John McClellan of Seattle Children’s Hospital in Washington emphasize the importance of the published findings. They write that “particularly worrying are both the data on the magnitude of weight gain and the conclusion that metabolic side effects are underestimated in those studies in patients already exposed to atypical antipsychotics. ” When a drug is submitted for regulatory approval, companies present results from placebo-controlled trials that involve chronic patients, Correl told the SRF website. These patients, with a high degree of probability, have already significantly gained weight as a result of the therapy.

In light of the findings, Correl and colleagues are calling for restrictions on the use of second-generation antipsychotics. Varley and McClellan agree: “Given the risk of weight gain and the long-term risk of cardiovascular and metabolic disorders, the current practice of widespread and increasing prescribing of atypical antipsychotics to children and adolescents should be reviewed.” They note that the use of these drugs is on the rise even despite the fierce controversy that has erupted over the growing number of diagnoses of bipolar disorder in children and adolescents. “Atypical antipsychotics are prescribed to children with bipolar disorder based on the adult literature,” with no evidence of a “continuum” linking adult and childhood forms of the disorder, they write.

The results suggest a need to consider less risky medications as well as non-drug options. However, Correll noted, despite the risks of second-generation antipsychotics, these drugs have brought stability to the lives of many people with severe mental illness. As a result, some are unwilling to try a different drug once they find one that families helps. He said that clinicians should educate them about side effects and lifestyle changes, such as exercise and shunning liquid calories, that could lessen their impact.

Correll thinks that clinicians should not only monitor height and weight at each visit, but also test for the “silent, unseen side effects” that may lead to cardiovascular disease. He and his colleagues recommend obtaining fasting blood work for glucose and lipids at baseline, three months, and every six months thereafter. Until researchers discover better drugs, he said, “We’re between a rock and a hard place.”—Victoria L. Wilcox.

Reference:
Correll CU, Manu P, Olshanskiy V, Napolitano B, Kane JM, Malhotra AK.