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Trintellix (Vortioxetine) & Weight Gain or Weight Loss?

Trintellix (Vortioxetine hydrobromide), formerly sold under the name Brintellix, is an antidepressant that was jointly developed by the pharmaceutical companies Lundbeck and Takeda.  In 2013, Trintellix received FDA approval for the treatment of major depressive disorder in the United States.  Trintellix is classified as a “serotonin modulator and stimulator” in that it functions as an inhibitor, antagonist, and agonist of various serotonin receptors.

More specifically, Trintellix inhibits the serotonin transporter (SERT); antagonizes 5-HT3 receptors; agonizes 5-HT1A receptors; and antagonizes 5-HT7 receptors.  Through its unique serotonergic action, many users of Trintellix find that the drug alleviates depressive symptoms.  However, some individuals are concerned with potential side effects of Trintellix, including body weight change (weight gain or weight loss).

Trintellix (Vortioxetine) & Weight Gain: Possible Causes

If you experience weight gain as a result of Trintellix, below are some potential causes.  Understand that the specific causes of weight gain among Trintellix users (who end up gaining weight) will be subject to significant individual variation.  Certain individuals might end up gaining weight because Trintellix increased their appetite (or reversed their poor appetite stemming from untreated major depressive disorder).  Others might end up gaining weight because Trintellix slightly altered their hormones and/or metabolism.

  • Appetite increase: It is known that, for a subset of individuals, untreated depression results in low appetite which might lead to low caloric intake, weight loss, and a potentially an underweight BMI. In the event that you had untreated depression and weren’t consuming much food because the depression interfered with your appetite, you might find that Trintellix alleviates your depression, which in turn, normalizes your appetite.  If your appetite normalizes (from a previously low appetite) while using Trintellix – you might consume more calories than you previously had been, and you may gain some weight.  That said, even if you didn’t have a low appetite before Trintellix, there’s a chance that the medication could enhance your appetite – possibly causing weight gain.
  • Bloating: Most people won’t gain a significant amount of weight while using Trintellix. However, among those who notice weight gain from Trintellix, it’s possible that bloating (or water retention is the cause).  Bloating may be related to changes in gut bacteria and/or gastrointestinal distress as a result of Trintellix treatment.  If you suspect bloating as a cause of your weight gain, realize that it’s probably not actual “fat gain,” rather, a bit of extra water retention.
  • Blood sugar changes: Some individuals might experience blood sugar changes as a result of Trintellix. Though blood sugar changes aren’t known to be a common side effect, any medication that alters central serotonergic neurotransmission alter the hypothalamic-pituitary-adrenal axis, which in turn, affects insulin sensitivity.  Deleterious changes to insulin sensitivity and/or blood glucose levels throughout treatment with Trintellix might increase your hunger and cause weight gain.
  • Constipation: A relatively common side effect of Trintellix is constipation, possibly resulting from decreased gastric motility. Constipation refers to difficulty emptying the bowels, and is usually associated with indigestion and hardened stools.  If you’re regularly constipated and/or become severely constipated while using Trintellix, this might explain your weight gain.  In other words, your body weight may be higher because you haven’t had a recent bowel movement.
  • Cravings: Some individuals taking Trintellix may notice an increase in cravings, particularly for unhealthy (hyperpalatable) foods, throughout their treatment. If you experience frequent or difficult-to-resist food cravings while taking Trintellix, the cravings might trigger you to eat more food (and total calories than usual), ultimately explaining your weight gain.  Many people report increases in sugar and/or carbohydrates while taking antidepressants – this could somehow be related antidepressant-induced changes in serotonin signaling.
  • Fat storage: It’s possible that antidepressant medications like Trintellix could interact with hormones and/or genes implicated in fat storage to increase the amount of body fat that’s stored during treatment. Though there’s no direct evidence that Trintellix alters body composition via increasing body fat gain, it’s possible that Trintellix could trigger increased fat storage in a subset of Trintellix users, ultimately accounting for some weight gain.
  • Fatigue: As a result of the serotonergic modulation exerted by Trintellix, some individuals may experience increased fatigue or lethargy throughout treatment. If fatigue and/or lethargy is significant, this might lead to decreased physical activity and energy expenditure throughout the day.  If Trintellix is making you tired or comfortably relaxed throughout the day to the point that you’ve become more sedentary than usual, this might account for any weight gain that you experience.
  • Gut bacteria: Taking Trintellix on a daily basis may negatively affect concentrations of gut bacteria or microbes. Any detrimental effects of Trintellix on gut bacteria could cause appetite increase, bloating, and even hormone changes – all of which may lead to weight gain.  If you’re experiencing gastrointestinal distress or gastric side effects, there’s a chance that your gut bacteria were altered from Trintellix – possibly explaining some of your weight change.
  • Hormone changes: Trintellix and other antidepressant medications may interact with hormone production throughout the body, possibly increasing or decreasing certain hormones that regulate body weight. For example, many suspect that serotonergic antidepressants like SSRIs lower testosterone.  If Trintellix is altering your body’s hormone production in an unfavorable way, you might lose some muscle and/or gain fat throughout treatment.
  • Lower motivation: Even if Trintellix treats your depression, you may end up with low motivation as a side effect. Some people using antidepressants report that the drugs make them feel emotionally numb and/or comfortably relaxed, such that they lack motivation to exercise or engage in physical activity.  If your motivation plummets while using Trintellix and this yields lower physical activity throughout the day, this could explain your weight gain.
  • Social eating: Certain individuals with untreated depression isolate themselves from social events with others such as going out to eat. However, if depression is effectively treated with Trintellix, the persons who formerly isolated themselves may become more social – ultimately doing more social things, including, dining out.  If you’re dining out more frequently since starting Trintellix, this may explain your weight gain.  Although dining out more frequently doesn’t guarantee weight gain, it could increase likelihood of weight gain due to the fact that caloric loads (and portion sizes) are usually exceptionally large at restaurants (compared to home-cooked meals).
  • Slowed metabolism: As a result of changes in hormone production, gut bacteria, and physical activity while using Trintellix, you may end up with a slowed basal metabolic rate (BMR). A slowed BMR from Trintellix means that your body is burning fewer total calories (less energy) throughout the day than usual.  Assuming Trintellix negatively affects your basal metabolic rate, this may be a reason as to why you’re gaining weight during treatment.
  • Taste enhancement: While taking Trintellix, you might notice that your taste improves or is enhanced compared to pre-treatment. In other words, foods end up tasting more delicious while using Trintellix compared to before using the drug.  Taste enhancement while using Trintellix may result from Trintellix-induced neurochemical changes, connectivity changes, and/or regional activation changes within the brain.  Assuming food ends up tasting better during treatment – you may have a difficult time putting down the fork.

Trintellix (Vortioxetine) & Weight Loss: Possible Causes

Although most people don’t end up experiencing significant weight change on Trintellix, a small percentage of individuals may report weight loss.  Included below is a list of potential reasons as to why someone might lose weight while using Trintellix.  Understand that the specific reasons that one Trintellix user loses weight during treatment may not be relevant to another.

  • Appetite reduction: Certain Trintellix users might notice that their appetite significantly decreases during treatment. Decreased appetite may be attributable to certain Trintellix side effects such as nausea and/or vomiting – let’s face it, it’s tough to eat food when you’re constantly nauseous.  In other cases, decreased appetite may be due to the fact that a person’s depression is now properly treated. Some people exhibit heightened appetites with untreated depression, and when treated, appetite decreases back to normal.  Regardless of why your appetite decreases on Trintellix, lower appetite usually results in decreased caloric intake – and weight loss.
  • Dehydration: If you experience a small amount of weight loss while using Trintellix, it may be explained by dehydration. Some individuals experience diarrhea and vomiting as side effects – each of which might lead to dehydration.  If you’re dehydrated and weigh yourself, you may see that you lost a few pounds on the scale.  That said, replenishing lost fluids by increasing water intake might get your weight back to normal.
  • Diarrhea: A common side effect of Trintellix is diarrhea, or the rapid passage of stools through the intestine. If you experience diarrhea, you may end up losing weight as a result of a laxative effect whereby your body isn’t absorbing the foods that you consume and excreting more water than usual.  Once you get the diarrhea under control, you may notice that your body weight returns to normal.
  • Energy & motivation increase: Certain Trintellix users will report significant increases in physical energy and/or motivation – compared to pre-treatment. If your energy level and/or motivation increases as a result of Trintellix, you may be more likely to engage in physical exercise throughout the day.  Assuming you’re exercising more while using Trintellix than before using it – you’ll likely end up losing weight.
  • Healthier food choices: When certain people are depressed, they may make unhealthy food choices such as eating hyperpalatable foods devoid of nutritional value (e.g. candies). Others with untreated depression may eat mostly fast-food because they’re too depressed or lack the energy to cook for themselves.  If Trintellix effectively corrects depressive symptoms, individuals who formerly made unhealthy food choices (e.g. fast food) may start caring about their personal health and wellbeing whereby they make healthier food choices.  Because healthier food choices are more satiating, those who eat healthier during treatment might consume fewer calories and lose some weight.
  • Metabolism increase: Some people may end up experiencing an increase in basal metabolic rate (BMR) while using Trintellix. An increase in BMR during treatment means that your body will be burning more calories than usual, possibly explaining your weight loss.  Increased basal metabolic rate may be attributable to increased physical activity or exercise during Trintellix treatment (due to heightened motivation).
  • Nausea: A fairly common side effect of Trintellix is nausea. If you become nauseous throughout treatment with Trintellix, the thought of consuming food may be unappealing.  Because nausea might lower appetite and lead to decreased caloric intake, those who experience nausea as a side effect of Trintellix may end up with weight loss.  Getting the nausea under control will generally result in body weight normalization.
  • Self-control: Depression can sometimes interfere with self-regulation or self-control such that we have a difficult time restraining ourselves around food and end up overeating. However, when the depression is treated with an antidepressant medication like Trintellix, our self-control may increase.  Better self-control means that you may have an easier time restraining yourself around food thereby minimizing likelihood of overeating.
  • Taste blunting: A very rare adverse effect of antidepressants like Trintellix is taste blunting. Taste blunting means that foods lack flavor and/or don’t taste as good as you remember.  If you experience blunted taste while using Trintellix, you may not want to eat as much food – which could explain your weight loss.
  • Vomiting: In addition to nausea, some individuals using Trintellix may end up vomiting. Vomiting not only can cause dehydration, but it can prevent your body from absorbing foods that you recently consumed.  For this reason, if you end up vomiting a lot during treatment, you could lose a bit of weight.  Getting the vomiting under control should help get your body weight back to normal.

Trintellix & Body Weight Change (Research)

Included below are data trials in which the effect Trintellix (vortioxetine) on body weight was documented.  Based on multiple reviews of the available drug data, it seems as though (for most users) Trintellix is unlikely to cause clinically significant weight gain or weight loss over the short-term and long-term.

2016: The safety and tolerability of vortioxetine: Analysis of data from randomized placebo-controlled trials and open-label extension studies.

Baldwin, Chrones, Florea, et al. analyzed data from randomized controlled trials and open-label extension studies in which vortioxetine (Trintellix) was administered.  In the analysis, researchers documented the effect of Trintellix on participants’ body weights.  As you’ll read, there didn’t appear to be any significant weight changes over the short-term (6-8 weeks) or long-term (up to 52 weeks) among Trintellix users – regardless of the dosage.

Short-term: Short-term trial data included 3018 adult patients treated with vortioxetine (5-20 mg per day) and 1817 patients treated with a placebo.  It was discovered that short-term treatment with Trintellix (6-8 weeks) resulted in no clinically significant body weight change compared to a placebo.  Results discovered that placebo users exhibited ~0.1 kg weight gain whereas vortioxetine users exhibited weight changes of -0.1 kg to +0.1 kg (with no dose-dependent effect).  It was noted that the incidence of clinically relevant weight gain (defined as at least 7% weight increase from baseline) was: 0% (15 mg users); 1.2% (10 mg users); and 0.6% for placebo users.  The incidence of clinically significant weight loss (defined as at least 7% weight decrease from baseline) was: 0.2% (5 mg users); 1.3% (20 mg users); and 0.6% for placebo users.

Long-term: Long-term trial data was extracted from 5 extension studies in which 1313 patients were treated with 5-10 mg vortioxetine (52 weeks) and 1144 patients were treated with 15-20 mg vortioxetine (51 weeks).  At trial endpoints, average weight change from baseline among participants was +0.8 kg (5-10 mg) and +0.7 kg (15-20 mg).  If converted from kg to lbs., this would equal +1.76 lbs. for 5-10 mg users and +1.54 lbs. for 15-20 mg users.  The incidence of clinically significant weight gain (defined as 7% body weight increase from baseline) was 13.3% of the 5-10 mg users and 11% of the 15-20 mg users.  The incidence of clinically significant weight loss (defined as 7% body weight decrease from baseline was 6.1% of the 5-10 mg users and 7.7% of the 15-20 mg users.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/26864543

2015: Profile of vortioxetine in the treatment of major depressive disorder: an overview of the primary and secondary literature.

Kelliny, Croarkin, Moore, and Bobo reported upon the effect of vortioxetine in the treatment of major depressive disorder.  In their report, researchers noted that vortioxetine treatment was not associated with clinically significant changes in body weight among adults with major depressive disorder – when administered over a short-term of 6 to 8 weeks.  Moreover, in a pooled analysis of short-term vortioxetine trials, clinically significant weight gain (or an increase of body weight by at least 7% from baseline) occurred in less than 3% of patients receiving vortioxetine at dosages within the range of 1 mg to 10 mg per day.

In long-term studies (~52 weeks), body weight change among vortioxetine users was modest (0.7-1.1 kg) and not clinically significant.  Researchers concluded that vortioxetine doesn’t appear to be associated with clinically significant changes in body weight.

  • Source: https://www.ncbi.nlm.nih.gov/pubmed/26316764

Based on the research, how much weight change will most Trintellix users likely experience?

Nothing significant.  The available short-term and long-term data from trials in which vortioxetine was administered to adults for the treatment of major depressive disorder reported no clinically significant weight changes among most users.  This considered, it is reasonable to suggest that most Trintellix users are unlikely to experience significant changes in body weight over a short-term (6 to 8 weeks) and long-term (up to ~1 year).  While it is possible that very long-term treatment (e.g. several years) might yield a different effect upon body weight than just ~1 year, this hypothesis isn’t substantiated by evidence.

  • Short-term users: Over the short-term of 6-8 weeks, vortioxetine users exhibit weight changes of -0.1 kg to +0.1 kg (regardless of the dose). In other words, most vortioxetine users might see their weight fluctuate by 0.22 lbs. (increase or decrease).  How likely is clinically significant weight change (defined as 7% body weight increase or decrease) over the short-term? Less than 1.3% of users experience clinically relevant body weight change with short-term vortioxetine use.
  • Long-term users: Over a long-term of ~52 weeks, vortioxetine users exhibit an average weight change of +0.7 to +0.8 kg. In other words, most vortioxetine users might see their weight increase modestly (1.54 lbs. to 1.76 lbs.) over the span of 1 year.  How likely is clinically significant weight change (defined as 7% body weight increase or decrease) over the long-term?  Clinically significant weight gain may occur in 11-13% of long-term vortioxetine users, whereas clinically significant weight loss may occur in ~7.7% of long-term vortioxetine users.

Variables that influence Trintellix (Vortioxetine) weight change

There are several variables that may influence the amount of weight change (gain or loss) that you experience while using Trintellix.  These variables include: prior substance use; genetics; lifestyle; concurrent substance use; duration of treatment; and Trintellix dosage.  It is the combination of these variables that likely determine which Trintellix users experience weight change – as well as its significance.

  1. Prior medication use: If you used antidepressant medications before Trintellix, there’s a chance that those medications may have caused weight gain or weight loss. If you took a medication that made you gain weight (prior to Trintellix), you may end up losing weight when you switch to Trintellix.  Oppositely, if you took a medication that made you lose weight (prior to Trintellix), you may end up gaining weight while using Trintellix.  In these cases, the weight gain and/or loss experienced after switching Trintellix will largely be due to homeostatic rebound effects (opposite of what was experienced on the prior medication).
  2. Genetics: Individuals who gain or lose a significant amount of weight while taking Trintellix may have genetics that differ from the majority of the population. For example, someone might have genetics that interact with Trintellix in a way that increases appetite or fat storage to a significantly greater extent than other users.  Though the specific ways in which genetics interact with Trintellix aren’t fully known, drug-gene weight interactions are likely.
  3. Lifestyle: Your lifestyle may also determine whether you’re prone to experiencing significant weight change while using Trintellix. If you aren’t getting adequate sleep, are highly stressed, are sedentary, and/or eat unhealthy foods – this may be a recipe for weight gain, regardless of the medication you’re using.  On the other hand, if you’re getting enough sleep, keeping stress low, are active, and eat healthy – you may end up losing weight during treatment.
  4. Concurrent substances: If you’re taking other medications or substances with Trintellix, there’s a chance that this may influence the weight change that you experience on Trintellix. First you must consider that the concurrent substances that you’re using may be causing weight change instead of Trintellix.  Then you must consider that there could be neurotransmitter-mediated, hormonally-mediated, and/or metabolism-mediated interactions (CYP450) between Trintellix and the other substance(s) that would explain weight change.
  5. Duration of treatment: Some individuals may experience weight changes after a short-term followed by weight stabilization, whereas others might experience no weight changes over a short-term followed by significant weight change over a long-term. In any regard, the total duration over which you’ve used Trintellix may influence how much weight you gain or lose.
  6. Trintellix dosage: Research suggests that there aren’t clinically significant effects of Trintellix dosage on body weight among users. That said, there may be individual variation in responses to dose on body weight.  Some individuals may experience a stronger weight loss or weight gain effect at a higher dose – than a lower dose.  Others might experience weight loss at a higher dose and weight gain at a lower dose.

Possible ways to minimize weight change on Trintellix (Vortioxetine)

Most people will not experience significant body weight changes while using Trintellix.  That said, if you are experiencing weight change (weight gain or weight loss) from Trintellix, below are some possible ways to minimize the unwanted weight change.  Realize that you should never implement any of these strategies without first consulting a medical professional to ensure that they’re safe.

  1. Track calories & activity: One thing many people don’t do is track their calories and record their physical activity. Tracking your calories and physical activity each day will help you understand whether you should be gaining, losing, or maintaining weight.  Most people can prevent significant weight gain or weight loss by eating maintenance calories.
  2. Manage side effects: Certain side effects like nausea, diarrhea, and vomiting can cause weight loss. Other side effects such as fatigue could cause weight gain in some cases.  If your side effects from Trintellix are culpable for your weight changes, it may help to get the side effects under control.  Once you’ve controlled your side effects, your weight may normalize.
  3. Dosage modification: Sometimes modifying your dosage of Trintellix may decrease weight change throughout treatment. Using the “minimal effective dose” will reduce the effect of Trintellix on your physiology which should lower likelihood of clinically relevant weight change attributable to the medication.
  4. Consider concurrent medications: If you’re experiencing unwanted weight change, you may want to evaluate the concurrent medications and/or substances that you use. Eliminating all medically-unnecessary substances that you’re using with Trintellix may help you get your weight recover to normal.  That said, adding concurrent medications (that are recommended by a psychiatrist) to be taken with Trintellix might also help keep your weight within a healthy range.
  5. Use for a longer-term: Certain Trintellix users get caught up in their weight change over a short-term. Because weight can fluctuate as the body adjusts to the medication (over a short-term), using Trintellix for a longer-term span may help you get a more accurate understanding of how it affects your weight.

Note: If you’re still unhappy with Trintellix weight gain or weight loss and nothing seems to help you get your weight back on track, you may want to talk to your doctor about Trintellix withdrawal and/or switching to another medication.  Although Trintellix stays in your system for a bit of time after discontinuation, your weight should gradually begin normalizing (over a period of weeks) once it has been eliminated.

Have you experienced weight changes on Trintellix?

If you’ve experienced weight gain or weight loss from Trintellix, leave a comment below.  In your comment, mention how much weight you gained or lost while using Trintellix.  Also note things like: how quickly you noticed the weight change (after starting treatment) and whether the weight change worsened, reversed, or self-corrected over a longer-term.  To help others get a better understanding of your situation, provide details such as: your Trintellix dosage; duration of Trintellix use; whether you use other substances (meds or supplements) with Trintellix; and note whether you’ve tracked your calories and physical activity throughout treatment.

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{ 2 comments… add one }
  • Tracy April 21, 2018, 10:10 pm

    It’s been about 3-4 weeks since I changed from Zoloft to Trintellix the thing I noticed is I am hungry all the time. I am already chunky and really don’t need to gain any more weight.

    I am going to my doctor on Monday and we will be discussing this I have also noticed I am more constipated than normal. I have had bloating in the abdominal area also not sure what that is from.

  • Lori March 28, 2018, 12:34 pm

    Since starting Trintellix, I have lost 5 lbs in about 6 weeks. I was taking Lexapro for 18 months before and noticed my weight continued to increase. I gained 10 pounds total while on Lexapro.

    I have not changed my eating or exercise habits so I attribute this the weight loss to Trintellix. I can say, I don’t feel I have the appetite I used to have.

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