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Invega (Paliperidone) & Weight Gain: What Should You Expect?

Invega (Paliperidone) is considered a newer spin-off of the antipsychotic Risperdal in that it contains the same active metabolite, but is thought to have fewer side effects and drug interactions.  It was initially approved in 2006 for the treatment of schizophrenia and was since granted approval for the treatment of schizoaffective disorder in 2009.  While the specific mechanism of action of Invega isn’t fully understood, it is believed to act as an antagonist at dopaminergic and serotonergic receptors.

Most notably, it is thought to act on D2 dopamine and 5-HT2 serotonin receptors as an antagonist.  It also elicits effects on H1 histamine receptors and the Alpha-1 and Alpha-2 noradrenergic receptors.  Invega is believed to work extremely well for the reduction of positive symptoms of schizophrenia such as hallucinations (e.g. hearing voices) and delusions (e.g. believing someone is out to get you).

Many users like the fact that Invega is manufactured in the form of extended-release (ER) tablets as well as an injectable form called “Invega Sustenna,” which delivers the drug for an entire month.  Despite the slight improvements of Invega over previous antipsychotics like Risperdal, most users still report side effects.  A relatively common side effect that users may experience while taking Invega is weight gain.

Invega and Weight Gain (Scientific Research)

The literature suggests that Invega is likely to cause clinically significant weight gain (characterized by at least 7% increase in baseline bodyweight) in between 8% to 10% of users. Over the short-term, it appears as though weight gain as a result of Invega ranges on average between 2.2 lbs to 4.4 lbs, whereas long-term weight gain is thought to be just under 5 lbs.  Suspected factors contributing to the weight gain include: appetite increases, baseline BMI, and prolactin.

2015: Researchers evaluated the efficacy of Invega Sustenna compared to a placebo for preventing relapse of schizophrenia symptoms.  A total of 305 participants were assigned to receive Invega Sustenna (160 participants) or a placebo (145 participants).  Participants received a 1-month formulation of Invega Sustenna at flexible doses, followed by a 3-month formulation for maintenance.

It was noted that the Invega Sustenna significantly delayed relapse of schizophrenia symptoms compared to a placebo.  Authors of the study noted that clinically significant weight gain occurred in 9% of those taking Invega compared to 3% of those taking a placebo.  This suggests that approximately 1 out of 11 participants experienced Invega-induced weight gain.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25820612

2015: A meta-analysis was published in 2015 determining the safety and efficacy of Invega ER to other second-generation antipsychotics.  All participants were Chinese and had been formally diagnosed with schizophrenia.  Researchers scoured the literature to find randomized-controlled trials (RCTs) of Invega ER and other antipsychotics to determine efficacy and adverse effects.

A total of 50 trials were included in the meta-analysis, and researchers noted that responses to Invega ER were superior to other antipsychotics.  In addition, it was noted that Invega ER was unlikely to trigger significant adverse effects.  Invega ER was also noted as being less likely to cause weight gain compared to other antipsychotics.

It should be noted that Invega was compared to “pooled antipsychotics” rather than each one individually.  Therefore it cannot be suggested that Invega is automatically superior to every other antipsychotic in terms of weight changes.  Also, increases in prolactin were considered similar to other antipsychotics, likely contributing to some weight gain.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/26229477

2015: A study published in 2015 compared 1-month injections of Invega Sustenna to various other oral antipsychotics taken daily for the treatment of schizophrenia in adults.  The study spanned over a duration of 15 months and was considered randomized.  A total of 444 participants were assigned to either Invega or another antipsychotic.

Symptomatic relapse and/or treatment failure over the course of 15 months was approximately 40% among those taking Invega Sustenna, compared to an estimated 54% among those taking other antipsychotics.  It was noted that weight gain was one of the five most common side effects of Invega Sustenna, occurring in 11.9% of users.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25938474

2015: A trial of 1-month Invega Sustenna injections was tested among 334 individuals with schizoaffective disorder compared to a placebo.  Results indicated that relapse rates were nearly double among those taking the placebo (33.5%) compared to Invega Sustenna (15.2%).  Despite the superior efficacy of Invega Sustenna compared to a placebo for the management of schizoaffective disorder, weight gain was noted in 8.5% of participants.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25562685

2015: A double-blind trial compared Invega ER to Abilify over the course of 26 weeks for the treatment of schizophrenia.  Flexible dosages were administered of both medications: Invega (3 mg, 6 mg, or 9 mg) and Abilify (2 mg, 5 mg, 10 mg, 15 mg). While neither drug was significantly more effective for reduction of symptoms compared to the other, weight gain was listed as a common adverse effect among those taking Invega ER.

This means that at least 10% of Invega ER users experienced weight gain, whereas this effect was not noted among those taking Abilify.  The results from this study suggest that weight gain may be much more common for users of Invega ER than Abilify.  It could be due to increased dopaminergic action compared to Abilify’s partial agonist effect at the D2 receptor.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/25617253

2014: A total of 311 adults diagnosed with schizophrenia or schizoaffective disorder were assigned to receive injections of Haldol Decanoate (25 mg to 200 mg) or Invega Sustenna (39 mg to 234 mg) every month for up to 2 years.  There wasn’t a significant difference in efficacy nor treatment failure when comparing the two drugs.  However, it was noted that individuals receiving Invega Sustenna gained weight after 6 months, whereas those receiving Haldol Decanoate actually lost weight (on average).

The reported weight gain caused by Invega Sustenna was approximately 4.78 lbs, whereas the loss on Haldol Decanoate was 2.11 lbs.  Further, those receiving Invega Sustenna had significantly greater levels of prolactin – a hormone associated with weight gain.  While weight gain was modest among those receiving Invega Sustenna, the prolactin increase may be more of a concern.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24846035

2013: A publication noted that atypical antipsychotics are thought to cause less side effects than typical antipsychotics.  Specifically, most atypical antipsychotics have low rates of extrapyramidal symptoms (e.g. akathisia) whereas typical antipsychotics are likely to carry unwanted extrapyramidal symptoms.  Despite having less extrapyramidal symptoms, many atypical antipsychotics carry risk of unwanted metabolic effects.

Examples of unwanted metabolic effects include: weight gain, increased blood sugar, and cholesterol increases.  Authors published a review of Invega ER to highlight its metabolic effects among those with schizophrenia.  They suggest that Invega ER is unlikely to carry adverse metabolic effects such as cholesterol and blood sugar changes.

That said, they did state the fact bodyweight increases ranging from 2.2 lbs to 4.4 lbs have been noted among users of Invega ER.  These bodyweight increases were suggested to have a dose-related relationship.  The weight increases should be considered modest and relatively benign should other metabolic biomarkers remain stable.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24241935

2013: Researchers conducted a comparative investigation of Invega ER and Zyprexa.  Effects compared included: metabolic profile, weight changes, insulin, and beta cell function.  A total of 80 participants received either Invega ER or Zyprexa for a total of 12 weeks.

Measures of bodyweight, subcutaneous fat, waist circumfrence, fasting blood sugar, insulin, cholesterol, prolactin, and triglycerides were collected at baseline, followed by every month thereafter.  Results suggested that both Invega ER and Zyprexa caused weight gain, increased waist circumference, elevated triglycerides, increased subcutaneous fat, and a higher levels of prolactin.  This study documents a need for tracking metabolic changes throughout treatment with atypical antipsychotics.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23559220

2013: A study published in 2013 tested the efficacy and tolerability of Invega as an antidepressant augmentation strategy for the treatment of refractory OCD.  A total of 34 adults received Invega along with an SSRI for 8 weeks in a double-blind trial.  Results indicated that Invega is tolerable and effective among certain individuals for the treatment of refractory OCD when added to an SSRI.

The results suggested that Invega did not cause clinically significant weight gain throughout the 8 weeks (only 0.3 lbs were gained on average).  Longer-term research needs to be conducted to confirm the efficacy and minimal weight gain suggested in this smaller-scale study.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/23842022

2011: Another study compared the effects of Invega ER to those of Zyprexa among individuals diagnosed with schizophrenia.  A total of 109 participants received Invega, whereas the remaining 106 received Zyprexa.  Results indicated that both medications were of equal efficacy for symptomatic management.

Bodyweight had increased an average of 3.3 lbs among those taking Invega ER and 4.4 lbs among those taking Zyprexa.  Appetite increases were noted in 8.8% of those taking Invega and 10% of those taking Zyprexa.  This suggests that Invega is capable of significantly increasing bodyweight and appetite.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/22969177

2010: A review of all studies investigating the tolerability of Invega was conducted.  Researchers gathered 15 articles, totaling 3,779 participants.  Evidence suggested that clinically significant weight gain was likely to occur in approximately 8% of those taking Invega.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20706126

2010: A meta-analysis analyzed the efficacy and tolerability of Invega ER compared to other atypical antipsychotics.  Placebo-controlled, randomized studies of Risperdal, Zyprexa, Seroquel, and Abilify were compared to those involving Invega ER.  Researchers determined that Invega ER carried lower likelihood of discontinuation for adverse effects – including weight gain.

This report suggests that weight gain isn’t likely among users of Invega ER compared to other atypical antipsychotics.  That said, this was an older report and weight gain has since been noted among users of Invega ER.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/20497747

2008: Researchers gathered data from randomized trials of Invega compared to a placebo.  Evidence suggested that Invega was effective for the treatment of psychosis and functional improvement compared to a placebo.  Adverse effects associated with Invega included: elevations in serum prolactin and weight gain – compared to a placebo.

Other data revealed that Invega wasn’t as likely to cause significant weight gain compared to Zyprexa.  Due to the fact that Zyprexa is known for being the most problematic antipsychotic in terms of weight gain, this isn’t really saying much.  Users should assume that Invega is capable of causing weight gain, with prolactin contributing to weight increases.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18425951

2008: When compared to Risperdal in short-term studies, Invega was found to have a similar adverse effect profile.  Both medications caused weight gain, extrapyramidal symptoms, and tachycardia more significantly than a placebo.  Results also indicated that prolactin levels significantly increase among those taking Invega compared to a placebo – possibly contributing to weight gain.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/18375569

2007: A study published in 2007 suggested that Invega was both safe and tolerable.  Researchers noted that it can cause “modest” weight gain at standard doses.  More substantial increases in weight were said to occur among those taking higher doses.  This means that among those taking doses between 6 mg and 12 mg – weight gain may be more likely and significant.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17927485

2007: An early study in 2007 suggested that discontinuation rates of Invega were comparable to a placebo.  In addition, this early report documented that Invega wasn’t associated with significant changes in metabolic biomarkers such as glucose, insulin, or lipids.  Elevations in prolactin levels were noted as were slight increases in bodyweight.

It was implied that those with higher pre-treatment BMIs gained less weight than those with lower BMIs.  Furthermore, weight changes from Invega were based on the administered dosage – the greater the dose, the greater the increase.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/17460786

How Invega Causes Weight Gain

There are many ways in which Invega ER (or Sustenna) could cause weight gain.  The research suggests that appetite increases, prolactin elevations, and fat storage are likely contributors to the weight gain.  That said, it is important to consider that factors contributing to weight gain may be subject to significant individual variation.

  • Appetite increase: One study suggested that approximately 8.8% of Invega users experienced an increase in appetite. Those that feel hungrier than usual as a result of the drug will have a tough time resisting the urge to eat extra food.  All of the extra calories consumed as a result of appetite increases will inevitably cause weight gain.
  • Blood sugar changes: While many studies suggest that blood glucose levels aren’t as likely to increase from Invega compared to other antipsychotics, it doesn’t mean that everyone maintains stable blood sugar levels while on this drug. Should your blood sugar increase during treatment with Invega, it may lead to significant weight gain.  This is due to the fact that blood sugar increases cause insulin to spike, ultimately signaling to the body to store more fat.
  • Fatigue: Many people taking antipsychotics experience debilitating fatigue. This fatigue may make it difficult to get out of bed in the morning or stay physically active.  Assuming you become fatigued, you probably will have a much tougher time getting to the gym, going on a walk, etc.  The increase in fatigue-induced sedentary behavior slows metabolism, burns less calories, and contributes to weight gain.
  • Fat storage: A study published in 2013 documented that Invega increases subcutaneous fat and increased waist circumference. This suggests that the body is storing more unhealthy fat as a result of the metabolic effects of the drug.  This increase in unhealthy fat storage translates to increases in bodyweight and promotes future weight gain.
  • Food cravings: Many users of Invega report increases in food cravings. These cravings may be fueled by increases in appetite, but not always.  Sometimes antipsychotics alter neurotransmission in such a way that you crave sugary foods (e.g. candy) and refined carbohydrates.  Assuming you cannot resist these cravings, it’s likely that you’ll gain some weight – possibly a lot.
  • Gut bacteria changes: Since Invega is known to alter lipid metabolism and gut bacteria are known to influence lipid metabolism, it could be that Invega directly alters gut bacteria – partially contributing to the lipid alterations. It is known that pharmaceutical agents change concentrations of gut bacteria, Invega likely has an impact on the gut microbiome.  The Invega-induced microbiome alterations likely cause weight gain.
  • Hormone levels: It is well-known that Invega causes significant increases in the hormone prolactin, even greater elevations than other antipsychotics. High levels of prolactin are associated with increases in bodyweight, whereas lower levels are associated with lower bodyweight.  In addition to prolactin causing weight gain, it is possible that Invega increases ghrelin (a hormone that causes us to feel hungry) and simultaneous leptin-resistance (preventing satiety).
  • Metabolism slowing: This drug may cause your metabolism to slow significantly compared to your homeostatic baseline. You may maintain the same dietary intake and exercise habits that you had prior to Invega, yet still gain weight.  This is due to the fact that your metabolism is slowing from the drug as a result of numerous neurophysiological changes.
  • Sedation: Certain people find that Invega causes sedation and makes them feel drowsier than usual. Assuming you feel increasingly sedated as a result of the medication, you may have a tough time getting sufficient physical activity to maintain a healthy metabolism.  Sedation may cause you to engage in lazy behavior and contribute significantly to weight gain.
  • Social eating: If the Invega is effectively managing your symptoms of schizophrenia, you may start to feel comfortable engaging in social activities. Many social activities involve food and going out to eat.  Going out to eat more frequently than usual is likely to cause weight gain as a result of larger portions and poorer food quality.
  • Taste improvement: Some people notice that Invega makes food taste better than it did before they used the drug. The taste improvement could be related to artificial adjustments of certain neurotransmitters.  Assuming everything you eat tastes significantly better than in the past, you may struggle to resist gorging on more food.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24446539

Does everyone gain weight on Invega?

No.  It is obvious that not everyone will gain weight on Invega.  In fact, a select number of individuals will end up losing weight on the drug, while many will remain “weight neutral” or experience no clinically significant change in bodyweight.  That said, clinically significant changes in bodyweight are considered at least 7% increases compared to pre-treatment baseline weight.

It is likely that many people gain weight, but since it’s under 7% of their baseline bodyweight – it isn’t reported as “clinically significant.”  Manufacturers of Invega (Janssen Pharmaceuticals) reports that likelihood of gaining weight is dose-dependent.  Specifically it is suggested that 7% of users gain weight at the 3 mg dose, 6% gain weight at the 6 mg dose, 9% at the 9 mg dose, and 9% at the 12 mg dose.

Understand that these percentages are based off of data from short-term (6 week) trials.  A long-term trial documented that significant weight gain occurred in up to 20% of users (that’s 1 out of 5).  Research suggests that those with lower baseline BMIs tend to gain more weight than those with higher baseline BMIs.

How much weight will you gain on Invega?

It is unknown exactly how much weight you will gain as an individual on Invega.  However, data from clinical trials suggests that weight gain may be dose-related.  Janssen pharmaceuticals unveiled the amount of weight gain based on the dosage of Invega administered over a 6-week term.

Short-term (6-weeks)

  • 3 mg = 1.3 lbs
  • 6 mg = 1.3 lbs
  • 9 mg = 2.2 lbs
  • 12 mg = 2.4 lbs

Long-term (6+ weeks)

When administered over a longer-term, it appears as though weight gain is more significant – as should be expected.  A study conducted over the course of 6-months reported that taking 10.8 mg Invega resulted in an average weight gain of 4 lbs among 104 users.  A 13-week trial documented average weight increases of 2 lbs to 3.3 lbs.

Anecdotal reports have suggested more substantial weight gain than has been reported in trials and research.  Understand that some people do not respond well to Invega, as evidenced by reports of 50 lbs weight gain in just 5 months – indicating an average of 10 lbs gained per month.

  • Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938305/

Factors that influence weight gain on Invega

It is important to consider the multitude of factors that influence weight gain on Invega.  These factors include things like dosage, duration over which you’ve been taking the drug, whether you are taking other drugs, your genetics, and lifestyle.

  1. Dosage

Some studies suggest that the dosage of Invega will influence the amount of weight you’re likely to gain.  In general, the greater the daily dosage (or strength of a monthly injection), the more weight you’ll end up gaining.  Those that are taking standard doses between 3 mg and 6 mg are less likely to gain weight compared to individuals taking doses between 9 mg and 12 mg.

For this reason, it is always recommended to take the minimal effective dose of Invega.  By taking the minimal amount necessary for symptomatic relief, you minimize the impact the drug has on your physiology.  Lower doses mean less significant alterations to neurotransmission, hormones, and other processes that may contribute to weight gain.

Keep in mind that dosage relative to bodyweight may predict weight gain.  Those that are smaller (height and weight) may experience more significant weight gain from a standard dose, compared to larger individuals (height and weight) taking the same dose.

  1. Time Span

There is adequate evidence to suggest that your odds of weight gain and the amount of weight you’re likely to gain depend on the time over which you’ve been taking Invega.  Those that take Invega over the short-term are less likely to gain significant weight compared to those taking it over a longer-term.  Studies suggest that short-term usage (6 weeks or less) resulted in modest weight gain between 2 lbs and 5 lbs.

Longer-term studies suggested slightly greater weight gain than short-term.  While it is possible that weight may stabilize, assuming the drug causes metabolic changes and/or appetite increases – the weight gain may be cumulative and substantial over time.  Furthermore, long-term users tend to increase dosage as a result of tolerance which can cause more weight gain.

  1. Interactions

In one study analyzing the efficacy of Invega along with an SSRI for the treatment of OCD, no significant weight gain was noted.  However, this study was extremely short-term with a small-sample size.  Since SSRIs are known to cause weight gain, and Invega is also capable of causing weight gain, it is important to consider the potential synergistic weight gain potential.

Both drugs may alter various physiological processes (e.g. hormone levels) that contribute to weight gain.  Assuming you are taking a multiple psychiatric drugs or a cocktail, consider that the combination may be causing greater weight gain than Invega as a standalone.  Moreover, ingestion of other substances such as illicit drugs and certain supplements may also cause weight gain synergistically with Invega.

  1. Genetics

Some antipsychotics will not cause weight gain among individuals with specific genetic polymorphisms.  Although at this time no specific genes have been identified to prevent weight gain among users of Invega, it should be considered that a subset of users may be protected from weight gain as a result of genetics.  If you have favorable genes, you may minimize the amount of weight you gain during treatment with Invega and/or you may end up losing some weight.

Other users may find that they gain a significant amount of weight and/or experience rapid weight gain.  These individuals may have unfavorable genes that don’t respond well to Invega – making substantial weight gain inevitable.  As more genes are identified as possible contributors, tests like GeneSight may be able to accurately predict whether you’ll gain weight on Invega.

  1. Lifestyle

While everyone likes to blame their medications for weight gain, not everyone likes to take responsibility for their lifestyle.  It’s easy to succumb to junk food cravings, be lazy instead of going to the gym, and stay up late instead of getting proper sleep.  To prevent weight gain on Invega and any antipsychotic, you should be eating an optimal diet, exercising daily, getting proper sleep, reducing stress, and staying busy.

Those with unhealthy lifestyle habits may end up gaining more weight from these habits than the drug.  In other cases, it is important to consider that the drug may act synergistically with unhealthy lifestyle choices to promote weight gain.  Most people are able to minimize weight gain by eating a healthy diet, exercising, and getting sufficient sleep (but not oversleeping).

Does Invega’s therapeutic benefit outweigh the weight gain?

Ultimately it will be up to you and your psychiatrist to decide whether Invega’s therapeutic benefit outweighs the amount of weight gain (and other side effects) you experience.  Some people will find that the drug works so well to manage positive symptoms of schizophrenia that they are willing to put up with significant weight gain.  Others may experience no symptomatic relief and pack on a lot of weight.

If you’re not getting substantial relief from symptoms with Invega, continued treatment probably isn’t justified.  Those that are getting moderate symptomatic relief, but pack on a serious amount of weight will have a tougher time considering whether to continue treatment and/or consider other options.  It is important to communicate with your psychiatrist, keeping a close eye on biomarker changes and bodyweight throughout treatment.

Individuals that experience mild symptomatic relief from Invega, but gain a lot of weight (or have other side effects) – may want to consider Invega withdrawal and/or another medication.  Communicate with your psychiatrist and inform them if the weight gain from Invega becomes a health and/or self-image concern.

Have you gained weight on Invega?

If you’ve taken Invega feel free to share a comment below discussing how it has affected your weight (gain, loss, or neutral).  Assuming you experienced a weight change, mention how much you gained and/or lost compared to your pre-treatment baseline.  To help others understand the specifics of your situation, share the dosage that you’ve taken, how long you’ve been taking Invega, and the format (ER vs. Sustenna).

For those that have experienced weight changes, how can you be sure they are from the Invega?  Did you keep all lifestyle habits the same pre-treatment and during treatment?  Have you considered that other medications could be contributing to weight changes you’ve experienced?

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{ 3 comments… add one }
  • Vincent Daut February 27, 2016, 2:53 pm

    I gained approximately 45 kilos in one year and a half and every month I lose a kilo and gain it again. Curse them with no mercy! Curse these doctors!

  • Weismanc18 June 9, 2016, 11:53 pm

    I have gained 70 pounds since starting Invega. This is in just under a year. I will be done taking it by 9 months from now. I hope to lose weight when I stop. Between the cravings, the slowed metabolism and the fatigue, I can’t compete. I do not feel like I can work out the way I used to, and it really bothers me. Hopefully I can lose this weight when I discontinue usage of this horrible drug.

  • Brwngoddess223 June 12, 2016, 10:36 pm

    I gained a total of 100 lbs while taking Invega Sustenna and come to find out I was misdiagnosed and I don’t even need the medication. I am so furious!! I lose a pound and I gained 2 back… And my boobs are huge!! I can’t wait until this drug is completely out of my system… I hope my post helps someone who is considering taking this medication…

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