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Fanapt (Iloperidone) & Weight Gain: What Should You Expect?

Fanapt (Iloperidone) is an antipsychotic that was approved in 2009 for the treatment of schizophrenia.  It functions similar to most current-market atypical antipsychotics in that it acts as an antagonist of the 5-HT2A receptor and D2 dopamine receptor.  It is thought to produce fewer extrapyramidal side effects (e.g. akathisia) compared to other antipsychotics.

The drug differs from other atypicals in that it affects a variety of other serotonergic receptors (5-HT1A, 5-HT2C, 5-HT6) and dopaminergic receptors (D3 and D4 receptors).  In addition, it affects neurotransmission of norepinephrine with effects on Alpha-1 receptors, with secondary noradrenergic effects on Alpha-2C receptors.  It is believed that noradrenergic function aids in ameliorating both negative symptoms and cognitive symptoms of schizophrenia.

With such a widespread mechanism of action, affecting serotonin, dopamine, and norepinephrine the drug isn’t associated with severe weight gain compared to other antipsychotics.  That said, it is still important to acknowledge that a small percentage of users will pack on a clinically significant (at least 7% of bodyweight) amount of weight during treatment.  Should you end up gaining weight from Fanapt, you may want to discuss alternative medications with your doctor.

Fanapt (Iloperidone) & Weight Gain (Scientific Research)

While earliest research of Fanapt suggested that the drug was unlikely to cause weight gain, newer reports suggest that it is associated with moderate weight gain.  The drug is associated with weight changes over the short-term (less than 12 weeks) and more weight gain over longer durations (over 12 weeks).  Weight gain was documented as being between 3 lbs and 7 lbs in research, with some studies highlighting comorbid increases in glucose and cholesterol.

2014: Researchers explored the drug Fanapt’s effects on various physiological biomarkers by summarizing the literature to date.  They initially discussed the fact that Fanapt significantly increased plasma glucose and the increase was dose-dependent.  Increases in plasma glucose are thought to be a possible contributing mechanism of drug-induced weight gain.

Results from an analysis suggested that clinically significant weight gain (characterized by at least 7% increases in bodyweight from baseline) occurred in approximately 12.3% of Fanapt users.  This was slightly greater than the other antipsychotic Risperdal and nearly double that of Haldol.  The greatest percentage of weight gain occurred among those taking high doses of Fanapt (between 20 mg and 24 mg daily).

Estimated average weight gain may have been related to dosage.  Those taking 4 mg to 8 mg gained an average of 3.30 lbs, those taking 10 mg to 16 mg gained an average of 4.62 lbs, while those taking 20 mg to 24 mg gained an average of 3.74 lbs.  Another study comparing the weight gain of Fanapt, Geodon, and a placebo – resulted in most significant weight gain with Fanapt at an estimated 6.17 lbs.

Clinically relevant weight gain was reported in approximately 21% of those taking Fanapt.  Researchers also reported that a 4-week study (double blind, placebo-controlled) of Fanapt for 25 weeks resulted in weight gain in approximately 9.2% of participants.  It was noted that weight gain was dose-dependent.  Authors note that Fanapt may be regarded as a drug that causes weight gain, especially among those taking high doses over a long-term.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24600226

2014: A review conducted in 2013 and published in 2014 analyzed a total of 121 articles regarding Fanapt.  Researchers noted that Fanapt was associated with low rates of extrapyramidal symptoms and akathisia compared to Risperdal and Haldol.  However, it was reported that 12% of users experienced clinically relevant increases in bodyweight.

The estimated 12% increases in bodyweight is relatively consistent with other research.  The evidence also suggested that the weight gain was most likely to occur during early stages of treatment.  Despite the weight gain, researchers were unable to unveil any significant physiological biomarkers that may have contributed to the increase.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24206391

2012:  Researchers published a study in 2012 comparing various antipsychotics for the treatment of schizophrenia and/or bipolar disorder.  They pooled together results from 56 trials, of which 11 assessed Fanapt.  It was noted that in short-term trials (spanning less than 12 weeks), statistically significant weight gain occurred in 4 trials of Fanapt (with 1,931 participants).

One short-term trial with 300 participants taking Fanapt reported an estimated weight gain of approximately 5.51 lbs.  In addition, a trial revealed that total cholesterol levels significantly increased by an estimated 11.60 mg/dL among those taking Fanapt (HDL increased by 3.6 mg/dL, while LDL increased by 10.30 mg/dL).  Elevations in glucose were reported in this trial, with estimated increases of 6.9 mg/dL.

It could be suggested that both cholesterol and glucose elevations as a result of Fanapt may contribute to weight gain.  While weight gain may not seem like much over the short-term, understand that it may amplify over an extended duration.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22900950

2012: A report from 2012 reviewed the potential of second-generation antipsychotics to cause both weight gain and glucose abnormalities.  It appeared as though Fanapt was associated with moderate risk of both weight gain and glucose dysregulation.  By comparison, researchers noted the drugs Zyprexa and Clozaril as having a higher risk.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22913904

2011: Another report of Fanapt documented modest weight gain among users.  Researchers suggested that the drug may have a favorable profile compared to other antipsychotics due to the fact that it is unlikely to affect glucose, lipid, and prolactin levels.  Further, they suggest that the drug may be ideally utilized among individuals who have difficulty coping with sedation and/or weight gain with other antipsychotics.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22217439

2010: A paper discussed the mechanisms of Fanapt’s action, suggesting that it acts mostly on the 5-HT2A receptor, followed by the D2 receptor as an antagonist.  In other words, it has a fairly similar primary mechanism of action to other atypical antipsychotics.  It was noted that Fanapt is thought to be equally effective as Haldol, Risperdal, and Geodon.

The drug had been tested on an estimated 3,200 individuals during trials.  Authors of the report suggest that Fanapt is considered to cause “minimal weight gain.”  This report was published just one year after real-world approval of Fanapt, therefore it is important to consider that weight gain may be more common than is implied.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20830317

2009: An early report after the drug’s approval suggested that Fanapt was associated with moderate weight gain; the specific amount was not mentioned.  Results from studies totaling over 3,000 participants suggested no significant changes in biomarkers of glucose, cholesterol, and triglycerides.  Understand that newer evidence suggests that elevated glucose and cholesterol resulting from Fanapt may be more common than was initially reported.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/19951132

2008: A randomized, placebo-controlled study assigned participants to receive Fanapt at one of several dosages: 4 mg to 8 mg per day (463 participants), 10 mg to 16 mg per day (456 participants), or 20 mg to 24 mg per day (125 participants).  These participants were compared to those taking a placebo (440 participants), Haldol (118 participants), and Risperdal (306 participants).  Among those taking Fanapt, average weight gain was 5.29 lbs.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18334911

2008: Prior to the approval of Fanapt, a short-term investigational report documented its safety.  Researchers collected studies from short-term trials spanning between 1998 and 2002.  It was noted that among those taking Fanapt, mild weight gain was reported (between 3.30 lbs and 4.62 lbs).  Understand that these trials were short-term (e.g. less than 12 weeks) and that weight gain may have been more significant over an extended duration.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18334908/

How Fanapt (Iloperidone) causes weight gain

It is certainly possible for Fanapt to cause clinically significant weight gain, defined as a weight increase of at least 7% of your baseline bodyweight.  In other words, if you gained 200 lbs, a clinically significant weight gain from Fanapt would be considered an increase to 214 lbs after you started taking the drug.  According to clinically published research, the specific mechanisms of how Fanapt causes weight gain aren’t fully understood, but below are some possible ways users may pack on the poundage.

  • Appetite increase: Some users may start taking Fanapt and notice that their appetite skyrockets. Assuming they weren’t getting proper treatment for their schizophrenia and are now medicated, their appetite may substantially increase.  The increase in appetite may stem from drug-induced neurochemistry alterations, but also from the fact that the person’s psychological functioning has normalized.
  • Blood sugar increase: Early reports suggest that Fanapt is unlikely to elevate blood sugars, but later studies document increases in plasma glucose following administration. It is well-understood that elevated levels of blood sugar can contribute to weight gain.  This affects insulin levels, and causes the body to pack on extra fat when you eat food – causing your weight to increase.
  • Fatigue: Certain users may find that the Alpha-1 noradrenergic stimulation from Fanapt is not enough to maintain high energy. Some users end up severely fatigued to the point that they struggle with getting out of bed or off the couch.  Assuming the medication depletes your physical and mental energy, it’s going to be tough to stay active to keep your metabolism high.
  • Fat storage: Some people may find that after taking Fanapt, their body begins storing excess fat in unpleasant areas. It may cause a build-up of belly-fat, love handles, or excess weight on the chest.  The increase in fat storage may be due to a combination of hormonal and neurotransmitter changes.  Specifically, blood sugar increases from the medication may spike insulin and cause your body to pack on the fat.  Furthermore, if the medication slows your metabolism, your body won’t be able to burn as much energy, and calories will get stored as fat.
  • Food cravings: You may find that Fanapt causes you to crave certain sugary, unhealthy foods. If you cannot hold yourself back from carbohydrates and sweets – it may be due to the changes in neurotransmission as a result of Fanapt.  These food cravings are difficult to resist for most, and as a result people end up eating unhealthy – leading to significant weight gain.
  • Hormone levels: While it is unclear as to whether Fanapt alters levels of ghrelin and leptin, many other atypical antipsychotics significantly increase ghrelin (the hunger hormone). When ghrelin levels are high, you feel hungry all the time.  Assuming Fanapt could be increasing ghrelin, you may feel incessantly hungry even if you just ate a big meal – thus increasing your chances of weight gain.  Further, it is important to consider that levels of other hormones such as testosterone, cortisol, and prolactin could be affected by Fanapt.
  • Metabolism slowing: Another mechanism that may contribute to significant weight gain is a slowing of your metabolism. If you naturally have a high baseline metabolism, taking this drug may slow it down significantly.  Assuming you maintain the same dietary intake as you had before taking Fanapt, weight gain is likely to ensue.
  • Motivational deficit: Certain individuals may find that Fanapt manages their symptoms of schizophrenia, but significantly decreases their motivation. While the noradrenergic overtones of the drug may increase motivation for some, others could end up feeling lethargic, low energy, and amotivational.  Should you experience a lack of motivation, you may cave to food cravings, fail to exercise, and engage in lazy behaviors.
  • Sedation: A side effect of Fanapt is sedation which makes it difficult to exercise and keep your metabolism high. Sedation often leads to increased resting, making it difficult to hit the gym or even go for a walk around the block.  Those that feel sedated may end up gaining weight due to the fact that they cannot overcome it to get proper exercise.
  • Social eating: Some people may experience such profound symptomatic relief from Fanapt that they start to engage in more social behaviors. They may hang out with friends, visit family, coworkers, and inevitably – go out to eat.  Going out to eat and/or social eating is a quick way to gain weight for anyone, not just those taking Fanapt.
  • Taste improvement: In some cases, people may perceive significant changes in their taste following administration of Fanapt. The drug may have altered certain neurotransmitters to the extent that food now tastes better than ever before.  The person may derive significant pleasure from eating and crave the dopaminergic increase associated with food consumption.  This artificially enhanced taste improvement may make food difficult to resist.

Note: For most people, weight gain associated with Fanapt may be due to a complex combination of the aforementioned factors.  In other words, the medication may slow metabolism, promote sedation, and simultaneously elevate blood glucose – all of which contribute to weight gain.  Keep in mind that the combinations of factors may be subject to significant individual variation.

Does everyone gain weight on Fanapt?

No.  Certainly not everyone will gain weight while taking Fanapt.  In fact, those that respond to the serotonergic and secondary noradrenergic mechanisms of the drug may find that they actually lose some weight.  Particularly those with a high BMI as a result of taking a more problematic antipsychotic like Zyprexa – which is known to significantly increase bodyweight.

Certain studies have documented that just over 9% of users will gain weight, while other research suggests that up to 21% of users gain weight on Fanapt.  Other reports estimate that approximately 12% of users will end up gaining a clinically relevant amount of weight from the drug.  Understand that many more users may gain a little weight, but it won’t be clinically significant.

How much weight will you gain on Fanapt?

Assuming you are in the minority of users (approximately 12%) who experience clinically significant weight gain, the amount of weight you gain will be based on numerous individual factors.  The research suggests that those who gain weight will pack on between 3 lbs and 7 lbs.  There may be a relationship between the amount of time you’ve been on the drug, the dosage, and the weight gain you experience.

Factors that influence weight changes on Fanapt

Like most atypical antipsychotics, there are a variety of factors that influence the amount of weight gain (or change) you experience while taking Fanapt.  The most prominent factors include: dosage and duration over which you’ve been taking the drug.  Others to consider include: medication interactions, genetics, and lifestyle.

  1. Dosage (12 mg to 24 mg)

Most people titrate their dosage of Fanapt up to between 12 mg and 24 mg daily for the management of schizophrenia.  Some research suggests that greater dosages of the drug may lead to more significant increases in bodyweight.  Therefore if you are taking the maximum dose of 24 mg, you may gain more weight than someone taking just 12 mg.

Keep in mind that to avoid weight gain, it is recommended to consider using the minimal effective dose.  Other factors such as the ratio of dosage to your baseline bodyweight and metabolism could influence weight gain.  Someone with a low bodyweight and slow metabolism that opts for the highest dose may gain significant weight on Fanapt.

  1. Time Span

The duration over which you’ve taken Fanapt can also influence the amount of weight you gain.  Those that have taken the drug since it was approved in 2009 may have gained more weight than someone who’s been taking it for just a couple months.  Weight gain can occur over the short-term, but is more likely to occur over a longer-term, especially if a dosage increase is required.

  • Short-term: Those taking the drug over a short-term (less than 12 weeks) may not gain as much weight as long-term users. That said, some studies documented weight increases of over 5 lbs in shorter-term trials.  Therefore it is important to be aware of how your body is reacting to the drug, even over the short-term.
  • Long-term: For some people, weight gain doesn’t increase over the long-term, but for others – the weight gain may exceed 7 lbs. Most research conducted with Fanapt hasn’t documented bodyweight changes over the course of several years.  Long-term administration may result in dosage increases and physiological changes that may amplify weight gain.
  1. Interactions

It is important to consider the possibility that other medications may be interacting with Fanapt to promote weight gain.  If you are taking a cocktail of psychiatric drugs, it will be difficult to determine whether the weight gain was from Fanapt, another drug, and/or from the synergistic effects of both.  Therefore, consider the fact that Fanapt may not necessarily be the culprit for weight gain – especially if you are taking another medication.

In addition, if you are taking other non-pharmaceutical supplements and/or drugs – it is important to consider the role that these may play in your weight increase.  Work with your doctor to determine the most plausible causes of your weight gain based on your specific medication and/or supplement regimen.

  1. Genetics

A study published in 2010 discovered that individuals with the -759C/T polymorphism (of the 5-HT2C receptor) don’t gain weight when taking Fanapt for over 7 months.  If you use a test like GeneSight, they may be able to determine whether you have this specific polymorphism and are genetically-immune to weight gain on this drug.  Those without this specific polymorphism are thought to be significantly more likely to gain weight.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20045196
  1. Lifestyle

It is important to avoid assuming that the drug is always responsible for weight gain.  While Fanapt may be causing you to pack on some weight, you should be making healthy lifestyle choices to minimize the amount of weight that you gain.  Consider the foods that you eat on a daily basis and whether your diet could be contributing to weight increases.

Also consider your stress level, the amount of sleep that you get per night, and your physical activity.  Something as simple as having a circadian rhythm imbalance can lead to increased production of ghrelin, ultimately contributing to weight gain.  Make healthy lifestyle choices so that you know whether the weight gain is truly from the medication.

Does Fanapt’s therapeutic benefit outweigh the weight gain?

Those who gain a significant amount of weight taking Fanapt may need to ask themselves whether the therapeutic benefit for management of schizophrenia outweighs the weight gain (and other side effects).  If you ended up gaining a little bit of weight such as 5 to 10 lbs after months of treatment, but the medication is effectively managing your symptoms – continuing with treatment is probably a good option.  However, if you pack on 15% of your bodyweight within a several months of treatment – you may want to consider Fanapt withdrawal and/or pursuing other options.

It is important to work with your psychiatrist and discuss any concerns you may have with increases in bodyweight and/or various other biomarkers such as heart-rate, blood glucose, hormones, and cholesterol.  Assuming the medication is working well, your psychiatrist may be able to come up with an augmentation strategy to minimize the drug-induced weight gain.  For most individuals with schizophrenia, moderate weight gain can be justified if the medication is working properly.

Have you experienced weight changes on Fanapt?

If you’ve taken Fanapt, be sure to leave a comment below mentioning whether you gained weight.  Discuss how long you had taken the medication (or have been taking it), as well as the dosage you’re taking.  To help others get a better understanding of your situation, document when you first noticed weight changes on Fanapt and whether these changes have continued throughout your treatment.

How are you able to pin the weight gain on Fanapt rather than other medications, supplements, or your lifestyle choices?  If you are taking other medications, have you considered the synergistic potential of weight gain?  For those that have undergone genetic testing, do you have the -759C/T polymorphism (of 5-HT2C) that prevents weight gain on Fanapt?

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