Aripiprazole, commonly known by the brand name Abilify, is an atypical antipsychotic medication used in the treatment of various mental health conditions, including schizophrenia, bipolar disorder, and major depressive disorder. While aripiprazole is often considered to have a lower risk of weight gain compared to other antipsychotics, it's important to understand its potential effects on weight and metabolism.
How Aripiprazole Affects Weight
The relationship between aripiprazole and weight is complex and can vary significantly from person to person. 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. Several factors influence how aripiprazole affects weight, including individual susceptibility, dosage, duration of treatment, and the presence of other medications.
Potential Mechanisms for 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.
- Increased Appetite: Some individuals report an insatiable appetite or constant hunger while taking aripiprazole. 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.
- Effects on Blood Sugar: 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.
- Metabolic Regulation: 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 H1 receptors and dopamine D2 receptors to regulate metabolism.
- Sedation and Reduced Activity: Abilify can cause tiredness and drowsiness that may make it difficult for you to stay motivated, get out of bed, or do exercise.
- Serotonin Receptor Activity: 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.
Aripiprazole and the 5-HT2C Receptor
One theory behind aripiprazole’s varying effects on weight gain is that, in the presence of high serotonergic activity, aripiprazole acts as an antagonist at the 5-HT2C receptor, thus increasing the potential for weight gain. Preliminary evidence suggests that aripiprazole is a partial agonist at 5-HT2C. In the presence of antidepressants with high serotonergic activity, aripiprazole may act as an antagonist at the 5-HT2C receptor, thus increasing the potential for weight gain. In environments with low serotonergic activity, aripiprazole may act as an agonist at the 5-HT2C receptor, thus having less effect on the potential for weight gain. This varying effect at the 5-HT2C receptor may explain why aripiprazole has not been associated with significant weight gain in previous studies focusing on schizophrenia and bipolar disorder.
A retrospective electronic medical record chart review of the Veterans Integrated Service Network (VISN) 22 Veterans Affairs (VA) database from January 1, 2003, until December 31, 2009, was performed after institutional review board approval (VISN 22 covers VA patients from all of Southern California and parts of Nevada). The chart review compared patients’ weight and body mass index (BMI) while taking aripiprazole alone (n = 1,177), versus aripiprazole plus a high-serotonergic antidepressant (citalopram, fluoxetine, paroxetine, sertraline, or venlafaxine; n = 145), versus aripiprazole plus a low-serotonergic antidepressant (bupropion; n = 77). Patients had to be on continuous treatment for a minimum of 6 months, with continuous treatment defined as having no breaks in treatment greater than 90 days (Figure 1). Data were extracted electronically through an automated process. Extraction was repeated to ensure quality control of the data. The baseline BMI was based on the last weight taken in the 180-day period prior to the start of aripiprazole monotherapy or combination drug therapy (T0). All 3 groups were relatively similar at baseline, with the exception of a difference in age, BMI, and sex (Table 1).
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Aripiprazole Compared to Other Antipsychotics
Most antipsychotic medications are associated with an increased risk of weight gain. A proposed mechanism is the antagonism at the 5-HT2C receptor, which has been associated with an increase in food intake. In contrast, agonism at the 5-HT2C receptor, as produced by fenfluramine and m-chlorophenylpiperazine, may lead to suppression of appetite. Tecott and colleagues developed a strain of mice lacking the gene for the 5-HT2C receptor. These mice demonstrated increased obesity.
To understand which of the drugs resulted in the most widening of waistlines, Sabé and his colleagues reviewed data from 52 randomized controlled trials that used fixed doses of either first- or second-generation antipsychotics. By identifying different results along a curve, the researchers were able to depict the effects of each antipsychotic on body weight.
Aripiprazole resulted in the least weight gain while olanzapine caused the most.
- 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.
- 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.
Individual Factors Influencing Weight Changes
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. 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. 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. 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.
Managing Weight Gain Associated with Aripiprazole
Factor in non-pharmacological interventions like healthy diet, nutritional counseling, regular physical activity and use of cognitive and behavioral strategies.
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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. 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.
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