Antipsychotic medications play a crucial role in managing conditions related to psychosis and other mental health disorders. However, like many psychiatric drugs, they often come with unwanted side effects, one of the most significant being weight gain. This article delves into the relationship between antipsychotics and weight gain, exploring the mechanisms involved, different types of antipsychotics and their varying effects, and strategies to mitigate this side effect.
Understanding Antipsychotics
Antipsychotic medications primarily treat conditions and symptoms related to psychosis. These drugs are also very important for treating other conditions, too.
How Antipsychotics Work
Antipsychotics function by modulating the activity of neurotransmitters in the brain, particularly dopamine and serotonin. By changing the balance of the chemicals in your brain, you may start to have fewer symptoms. If these chemicals are out of balance, you may develop symptoms of psychosis like hallucinations and delusions. Scientists are still learning exactly how antipsychotics help.
Types of Antipsychotics
There are three main types of antipsychotic medications:
- First-Generation Antipsychotics: These block the way your brain uses several neurotransmitters, especially dopamine. They also block acetylcholine, histamine, and norepinephrine from latching onto various receptors.
- Second-Generation Antipsychotics: These medications block receptors like serotonin and dopamine. And they activate other serotonin and dopamine receptors.
- Next-Generation Antipsychotics: This new medication targets psychosis differently. It attaches to specific acetylcholine receptors that are only in your brain and affect memory and cognition. In clinical trials, it reduced schizophrenia symptoms.
Antipsychotics can also be categorized into two classes: typical and atypical antipsychotics. Both classes can cause weight gain, but they differ in that atypical antipsychotics cause fewer movement disorder side effects.
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The Link Between Antipsychotics and Weight Gain
Antipsychotics affect the chemical messengers in the brain associated with appetite control and energy metabolism, namely serotonin, dopamine, histamine, and muscarinic receptors.
Neurotransmitter Imbalance
All of these medications increase serotonin levels in the brain. Serotonin regulates mood and affects appetite, yet this can have varying results depending on the length of treatment. Short-term use reduces impulsivity and increases satiety, which can reduce food intake and cause weight loss. However, long-term use (longer than a year) can cause downregulation of serotonin receptors, which subsequently causes cravings for carbohydrate-rich foods such as bread, pasta, and sweets that ultimately may lead to weight gain.
Metabolic Changes
In addition to causing weight gain, antipsychotics can also impair glucose metabolism, increase cholesterol and triglyceride levels, and cause hypertension, all of which can lead to metabolic syndrome and worsen obesity-related diseases.
Variability in Weight Gain Among Antipsychotics
The extent of weight gain varies among different antipsychotic medications. A study reviewed data from 52 randomized controlled trials that used fixed doses of either first- or second-generation antipsychotics to understand which of the drugs resulted in the most widening of waistlines. The researchers identified different results along a curve, and were able to depict the effects of each antipsychotic on body weight.
- Quasi-parabolic: Antipsychotics along this curve-including brexpiprazole, cariprazine, haloperidol, lurasidone, and quetiapine ER-caused an initial weight gain at a relatively low dose and increased with increasing doses. But at a certain point, the numbers on the scale stabilized, even at higher doses.
- Plateau: With the drugs in this group, there was a dose above which weight gain did not increase any further; weight did increase up to a certain point, but after that, adding more of the drug did not lead to an increase of any additional pounds. The average weight gain from these medications-including asenapine, iloperidone, paliperidone LAI, quetiapine IR, and risperidone-ranged from three to nearly six pounds.
- Ascending: In this last group, weight gain continued to climb with each increasing dose, with an average gain from two to nearly 9.5 pounds. The drugs on this curve included aripiprazole, olanzapine, risperidone, and paliperidone, in both oral and long-acting injection forms. Aripiprazole resulted in the least weight gain while olanzapine caused the most.
The Role of Ghrelin
“It seems that ghrelin has an orexigenic role that is directly implicated in antipsychotics-induced weight gain,” he said. “Second generation antipsychotics can act on ghrelin secretion and therefore increase appetite. Some antipsychotics, such as olanzapine and clozapine, presented the worst profiles and can ultimately send patients down a path towards metabolic syndromes, Sabé said. Lurasidone may offer the best case scenario, he added.
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Strategies to Minimize Weight Gain
For people taking psychiatric medications for mental health, there are strategies to minimize weight gain. Optimizing lifestyle and daily habits is important.
Lifestyle Modifications
- Eating a healthy diet with whole foods and limiting processed foods and added sugars.
- Staying physically active. Physical activity, in particular, can have a double effect of both improving mental health and minimizing weight gain that might otherwise occur.
- Minimizing stress.
- Ensuring adequate restful sleep.
Medication Management
Another strategy to minimize weight gain is to work with your healthcare provider to determine if there might be an appropriate alternate medication option with a lower risk of weight gain. In addition, the anti-diabetes medication metformin has been shown to be effective in treating and preventing psychotropic-induced weight gain.
Comprehensive Approach
Factor in non-pharmacological interventions like healthy diet, nutritional counseling, regular physical activity and use of cognitive and behavioral strategies.
Other Psychiatric Medications and Weight Gain
While antipsychotics are strongly associated with weight gain, it's important to consider other psychiatric medications.
Antidepressants
All of these medications increase serotonin levels in the brain. Serotonin regulates mood and affects appetite, yet this can have varying results depending on length of treatment. Short-term use reduces impulsivity and increases satiety, which can reduce food intake and cause weight loss. However, long-term use (longer than a year) can cause downregulation of serotonin receptors, which subsequently causes cravings for carbohydrate-rich foods such as bread, pasta, and sweets that ultimately may lead to weight gain.
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Anxiolytics and Sleep Aids
There is no clear link between traditional anti-anxiety medications such as benzodiazepines and weight gain. Similarly, not all medications for sleep cause weight gain; one that has been associated with weight gain is diphenhydramine (the active ingredient in Benadryl that is also used in many over-the-counter sleep aids). Diphenhydramine can contribute to weight gain by causing increased hunger and tiredness, which can make a person less active.
Mood Stabilizers
Mood stabilizers are often used to treat bipolar disease, and can increase appetite or cause changes in metabolism.
Stimulants
Stimulants are not likely to cause weight gain. In fact, many of them reduce appetite and can cause weight loss as a side effect.
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