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Fetzima (Levomilnacipran) & Weight Loss vs. Gain

Fetzima (Levomilnacipran) is a medication prescribed for the treatment of major depressive disorder in adults.  Although it is similar to the drug Savella (Milnacipran), Fetzima exhibits unique pharmacodynamics in that it functions as a serotonin-norepinephrine reuptake inhibitor (SNRI) with a 2-fold affinity for norepinephrine reuptake inhibition – relative to serotonin reuptake inhibition.

In other words, Fetzima exhibits a 1:2 ratio of serotonin to norepinephrine reuptake inhibition – such that it raises extracellular concentrations of norepinephrine to a greater extent than serotonin.  As a noradrenergically-dominant medication, many users report enhanced cognitive function and increased energy levels – sometimes accompanied by a reduced appetite.

Considering its mechanism of action and propensity to increase energy levels, many users wonder whether Fetzima can cause or promote weight loss.  Although there’s no strong evidence to substantiate the idea that Fetzima causes weight loss OR weight gain – it’s possible that the medication might induce weight change in a subset of users.

Does Fetzima cause weight change? (Loss or Gain?)

Not usually.  Most research indicates that Fetzima is a “weight neutral” antidepressant medication in that it is unlikely to induce clinically-relevant weight change relative to a placebo control – regardless of whether administered for a short-term (~8-10 weeks) or a long-term (up to 48 weeks).  That said, nearly all studies indicate that Fetzima can cause clinically-insignificant (probably unnoticeable) weight loss in users.

Fetzima treatment duration vs. body weight

  • Short-term: -1.01 lbs. to -1.69 lbs. – When administered for a short-term (8-10 weeks), Fetzima is associated with a minor reduction in body weight.
  • Long-term: –1 lbs. to -1.21 lbs. – When administered for a moderate-term (24 weeks) or long-term (48 weeks), Fetzima is associated with a minor reduction in body weight.

How many Fetzima users experience “significant” weight change?

In a large-scale 48-week open-label trial conducted by Mago et al. (2013), approximately 27% of Fetzima users experienced clinically significant weight change during treatment.  Clinically significant weight change is characterized as a body weight change (increase or decrease) of at least 7% from baseline (pre-Fetzima) weight.

  • Weight gain: 10% of users – This study reported that around 10% of Fetzima users exhibited clinically significant weight gain (or a body weight increase of at least 7% from baseline) over a 48-week span.
  • Weight loss: 17% of users – This study reported that around 17% of Fetzima users exhibited clinically significant weight loss (or a body weight reduction of at least 7% from baseline) over a 48-week span.

A review of the Fetzima trials by Asnis and Henderson (2015) reported an average weight loss of ~1.1 lbs. (0.5 kg) in 4 of 5 short-term (~8 week) trials – and average weight losses of ~1.1 lbs. (0.5 kg) and ~1.21 lbs. (0.55 kg) in longer-term 48-week and 24-week trials, respectively – among Fetzima users.  In all of the trials in which Fetzima users exhibited minor weight reduction – placebo users exhibited minor weight increases.

A study by Bakish et al. (2014) involving 186 Fetzima recipients (40 mg and 80 mg per day) reported clinically-insignificant weight losses of ~1.1 lbs. (40 mg/day) and ~0.88 lbs. (80 mg/day) relative to 185 placebo recipients (who experienced slight weight gain) – over an 8-week duration.  Another study by Gommoll et al. (2014) reported a modest average weight loss of ~1.01 lbs. in Fetzima users (40-120 mg per day) versus placebo users (who gained 0.26 lbs.).

An 8-week trial by Sambunaris et al. (2014) with 434 participants also reported a slight weight reduction of ~1.98 lbs. among Fetzima users (40-120 mg per day).  Data from a 24-week study by Shiovitz et al. (2014) involving 348 patients indicated that Fetzima (40-120 mg per day) users experienced an average weight loss of ~1.1 lbs. – whereas placebo users gained 1.1 lbs.

As was already discussed, a 48-week open-label trial by Mago et al. (2013) with 384 participants documented clinically significant weight change in 27% of Fetzima users (40-120 mg per day); 10% experienced significant weight gain and 17% experienced significant weight loss.  However, the average weight change among all Fetzima users was a weight loss of ~1.21 lbs.

An earlier 8-week trial by Asnis et al. (2013) reported average weight losses among fixed-dose Fetzima users of: ~1.1 lbs. (40 mg/day dose); ~1.69 lbs. (80 mg/day dose); and ~1.65 lbs. (120 mg/day dose) – and an average weight gain among placebo users of 0.41 lbs.  Moreover, a 10-week trial by Montgomery et al. (2013) documented zero significant weight change among Fetzima and placebo recipients.

Overall, all data are consistent in suggesting that Fetzima is a weight neutral antidepressant – regardless of treatment duration (short-term vs. long-term) and dosing (low-dose vs. high-dose).  While clinically significant weight change can occur in a small percentage of Fetzima users (27%; 17% lose weight vs. 10% gain weight), all data indicate that Fetzima is most likely to cause a clinically-insignificant (probably unnoticeable) weight loss of ~1 to 1.7 lbs.

Fetzima & Weight Loss (How It Could Occur)

Despite the fact that Fetzima isn’t associated with significant body weight change – this doesn’t mean that every single user experiences zero weight change.  Many Fetzima users will experience modest (clinically insignificant) weight loss – and a small percentage (~17%) of Fetzima users might experience clinically significant weight loss during treatment.

Because Fetzima exerts a strong noradrenergic effect, it’s not unreasonable to speculate that this mechanism could induce or promote weight loss in a subset of users.  The noradrenergic effect of Fetzima might promote weight loss by: reducing appetite; speeding up metabolism; increasing energy (to exercise); and enhancing willpower (to resist excess calorie intake).

Appetite decreases: Some individuals may experience decreased appetite or loss of appetite while using Fetzima.  The appetite reduction might occur as a result of hypothalamic modulation, increased noradrenergic tone (and anxiety), and/or other Fetzima side effects such as nausea, upset stomach, or vomiting.

In the event that your appetite is reduced or suppressed from using Fetzima – this might lead you to consume fewer calories (versus pre-treatment) such that you end up losing weight.  If the appetite reduction is maintained for a long-term, clinically-significant weight loss might occur.

Cognitive enhancement: Fetzima is a medication that many claim is able to enhance cognitive abilities.  Although cognitive enhancement will not directly cause weight loss, it might indirectly promote weight loss in a subset of users.

If aspects of cognition associated with impulse control and planning end up improving while using Fetzima – this might lead to weight loss by making it easier for a user to: (1) resist unhealthy foods and (2) plan healthy meals for weight management.

Energy increase: A post-hoc analysis of Fetzima trials suggests that Fetzima is an effective medication for attenuating fatigue associated with major depressive disorder – regardless of the user’s age or sex.  The fatigue-reducing properties of Fetzima should be expected – given that it exerts a potent noradrenergic effect which increases mental and physical arousal.

Assuming Fetzima reduces your fatigue or increases your energy levels – this might lead users to engage in exercise and/or increase their non-exercise activity thermogenesis – each of which could yield weight loss. (Read: https://www.ncbi.nlm.nih.gov/pubmed/26584326).

Gut bacteria modulation: Though the effect of Fetzima on gut bacteria hasn’t been investigated, it is known that neuropsychiatric medications can have a profound effect upon gut bacteria.  It is also understood that signals are transmitted bidirectionally between gut bacteria and the brain via the vagus nerve.

Assuming the actions of Fetzima favorably modulate gut bacteria, this modulation might result in appetite reduction, increased postprandial satiety (“feeling full”), and fewer food cravings – all of which could lead to weight loss.  Additionally, because gut bacteria may interact with hormones, favorable gut bacteria changes might reduce body fat storage and/or decrease water retention – possibly accounting for weight reduction in some users.

Hormonal modulation: Another potential means by which Fetzima might promote weight loss is by altering hormone concentrations.  Altering hormone concentrations can affect things like: (1) water retention; (2) metabolic rate; (3) fat storage; and (4) muscle synthesis – each of which can influence body weight and composition.

It isn’t fully understood how Fetzima might alter hormone concentrations, however, it is thought that Fetzima could upregulate sympathetic nervous system function via its noradrenergic effect to promote the release of stimulatory hormones (some of which are deficient in obese persons).  This potential hormonal modulation induced by Fetzima could promote fat burning, increase metabolic rate, and reduce excessive water retention – for weight loss.

Mood enhancement: Persons with major depressive disorder often sleep excessively, exhibit fatigue or lethargy, and struggle to engage in physical exercise.  Moreover, many individuals with major depressive disorder eat excessive amounts of unhealthy (hyperpalatable foods) as a coping mechanism (which leads to weight gain).

Assuming Fetzima effectively treats a preexisting major depressive disorder, the resulting mood enhancement might increase energy levels and motivation to exercise – and simultaneously decrease engagement in binge eating (as a coping mechanism or depression-induced behavior).  Mood enhancement might lead a subset of individuals to take better care of themselves (eating healthier, exercising, etc.) – possibly resulting in weight loss.

Nausea & vomiting: Nausea has been reported as being one of the most common side effects of Fetzima treatment (with some studies reporting this reaction in ~16% of users).  If you constantly feel nauseous, this nausea might interfere with your appetite to the extent that you don’t want to eat as much food (as you did before treatment).

Decreasing your calorie intake as a result of nausea-mediated appetite suppression could induce weight loss (especially if maintained over a long-term).  Additionally, if nausea is extreme enough to provoke vomiting, the act of vomiting might induce weight loss as a result of: appetite reduction; suboptimal food absorption; and/or dehydration.

Sweating: A fairly common side effect of Fetzima is excessive sweating or hyperhidrosis.  If you’re sweating excessively while using Fetzima, it’s possible that this side effect could lead to weight loss due to dehydrating the body.

Because most people carry a significant amount of water weight (especially persons who are overweight, consuming high dietary sodium and/or a high carbohydrate diet) – a substantial amount of water weight might be lost via hyperhidrosis.  Although the sweating-induced weight loss won’t be “fat loss” – it’s still a form of weight loss that deserves a mention.

Could Fetzima cause weight gain? (Possible ways)

Yes.  Although the “average” response to Fetzima is (clinically irrelevant) weight loss (~1 lb. to ~1.7 lbs.), a 48-week open-label trial documented “clinically significant” weight gain (at least 7% body weight increase from baseline) in 10% of users.  Considering this finding, it is reasonable to speculate that a small percentage of Fetzima users could experience some unwanted weight gain during treatment.

That said, it isn’t exactly clear as to how Fetzima causes weight gain a subset of users.  Potential explanations for Fetzima-induced weight gain might include:  increased appetite; cognitive dysfunction; constipation; food cravings; gut bacteria changes; and social eating.

  • Appetite increase: Although appetite reduction is a common side effect of Fetzima, increased appetite has not been documented as a side effect in medical literature. Nevertheless, if you’re experiencing an increased appetite while taking Fetzima – it’s likely that this reaction could lead to you consume more food than usual such that you gain weight.
  • Constipation: Clinical trials of Fetzima have reported constipation as a common side effect (occurring in ~9% of users). If you experiencing constipation from ongoing treatment with Fetzima, the constipation might cause a transient increase in body weight – along with bloating.  In the event that constipation is culpable for your weight gain, treating the constipation should result in weight normalization.
  • Cognitive dysfunction: Though Fetzima can enhance cognitive function for some users, others may report cognitive dysfunction such that the medication causes brain fog and erratic or unclear thinking. If you experience deficits in aspects of cognition that influence impulse control, feeding behavior, and/or motivation to maintain a healthy weight – you might end up gaining weight because you’re unable to resist unhealthy, calorically-dense foods.
  • Depression reversal: It is understood that certain individuals with major depressive disorder experience low appetite such that they under-eat, lose weight, and exhibit unhealthily-low body weights. Among persons who are underweight prior to using Fetzima, the medication might reverse depressive symptoms whereby appetite increases, caloric intake increases, and healthy weight gain ensues.
  • Food cravings: Fetzima is not known to induce food cravings (for most users). In fact, some users have documented that Fetzima significantly reduces preexisting food cravings.  That said, if Fetzima somehow increases food cravings – and you cannot resist these cravings, you may end up overeating and gaining weight.
  • Gut bacteria modulation: As was already mentioned, neuropsychiatric medications can alter gut bacteria (in beneficial and deleterious ways). If Fetzima induces deleterious changes to gut bacteria composition, this could promote weight gain via: increased fat storage, increased water retention, increased appetite, reduced metabolic rate, and/or decreased satiety.
  • Hormonal modulation: Ongoing treatment with Fetzima may alter concentrations of hormones throughout the body to promote weight gain. Though the effect of Fetzima on hormones hasn’t been fully investigated, some speculate that it might alter: testosterone, estrogen, cortisol, leptin, ghrelin, adiponectin, et al. – in ways that promote fat gain, water retention, and weight gain.
  • Social eating: If Fetzima successfully treats your depression, it’s possible that the resulting antidepressant effect might lead you to partake in a greater number of social activities – compared to when you were depressed. Because dining out (or “going out to eat”) is a popular social activity, it’s possible that an increase in the frequency of social eating/dining (as a result of Fetzima-induced mood enhancement) explains your weight gain.  After all, most restaurants serve large portions of calorically-dense food.
  • Taste improvements: When depressed, some individuals report a dulling of the senses, including taste. If your taste perception was limited while depressed, but Fetzima effectively treats your depression – then you might experience taste improvement, which could spur your appetite and calorie intake – inevitably leading to weight gain.

Note: There might be alternative explanations as to why someone could experience weight change (gain or loss) while using Fetzima (from the possibilities outlined above).  If you know of additional mechanisms by which Fetzima might promote weight change, share them in the comments.

Fetzima & Weight Change (The Research)

Included below are studies in which the effect of Fetzima on body weight was documented and/or discussed.  As of current, nearly all data are congruent in suggesting that Fetzima (Levomilnacipran) is a “weight neutral” medication such that it is unlikely to cause significant weight loss or gain – among users.

Though there are probably limitations associated with some of the studies included below, there are zero scientific data to suggest that Fetzima treatment induces clinically-significant weight change (at least 7% increase or decrease from baseline).  That said, there are data to support the idea that Fetzima might cause clinically-insignificant weight loss.

2015: Levomilnacipran for the treatment of major depressive disorder: a review.

Asnis and Henderson authored a review of the medication Levomilnacipran for the treatment of depression and discussed its pharmacodynamics (relative to other antidepressants) and its efficacy, safety, and tolerability – based on 5 short-term, double-blind, placebo-controlled studies and 2 long-term studies.  Upon reviewing available data from the aforestated studies, researchers stated that Levomilnacipran is “weight neutral” (such that it doesn’t significantly affect body weight).

That said, researchers highlighted that 4 out of 5 short-term Levomilnacipran trials documented clinically insignificant weight loss.  Average weight loss reported in 4 of the 5 short-term Levomilnacipran trials was ~1.1 lbs. (0.5 kg) – whereas the placebo was associated with weight gain of 0.22 lbs. (0.1 kg).

In the 2 long-term studies that were reviewed, Levomilnacipran was associated with an average weight loss of ~1.1 lbs. (48-week open label study) and ~1.21 lbs. (24-week randomized controlled trial) – respectively.  The clinically insignificant weight change led researchers to conclude that Levomilnacipran is a weight neutral medication when administered over a short-term (8 weeks) and long-term (24 to 48 weeks).

2014: Levomilnacipran ER 40 mg and 80 mg in patients with major depressive disorder: a phase III, randomized, double-blind, fixed-dose, placebo-controlled study.

Bakish et al. conducted a 10-week, double-blind, placebo-controlled, fixed-dose (40 mg and 80 mg) trial in which Levomilnacipran ER (extended-release) was administered to adult outpatients with major depressive disorder.  The intent-to-treat (ITT) population consisted of 3 groups: placebo (185 patients); Levomilnacipran 40 mg/day (186 patients); and Levomilnacipran 80 mg/day (188 patients).

At the end of the trial, it was apparent that Levomilnacipran did not cause clinically-significant weight change among users.  Results revealed that placebo recipients (185 patients) exhibited an average weight gain of ~0.22 lbs. (0.1 kg) – whereas Levomilnacipran recipients (40 mg/day and 80 mg/day) exhibited average weight reductions of ~1.1 lbs. and ~0.88 lbs., respectively.

2014: A randomized, double-blind, placebo-controlled study of flexible doses of levomilnacipran ER (40–120 mg/day) in patients with major depressive disorder.

Gommoll et al. reflected upon the safety, efficacy, and tolerability of flexible-dose (40 mg to 120 mg) Levomilnacipran ER (extended-release) in a Phase III randomized controlled trial among 355 patients with major depressive disorder.  The trial was considered short-term in that it incorporated just an 8-week treatment phase followed by a 2-week taper phase (off of the medication).

Although Levomilnacipran treatment was associated with side effects such as nausea (17%) and headache (16%), it was not associated with clinically-relevant weight change.  Levomilnacipran ER recipients exhibited an average weight loss of ~1.01 lbs. (0.46 kg), whereas placebo recipients exhibited an average weight gain of ~0.26 lbs. (0.12 kg).

2014: A phase III, double-blind, placebo-controlled, flexible-dose study of levomilnacipran extended-release in patients with major depressive disorder.

Sambunaris et al. conducted a Phase III randomized controlled trial evaluating the effectiveness, safety, and tolerability of Levomilnacipran ER (40 mg to 120 mg) as a treatment for major depressive disorder in 434 adults.  The trial implemented a 1-week single-blind, placebo-run-in phase followed by an 8-week double-blind phase and 2-week tapering period.

Among the 214 patients who received the placebo, weight change from baseline was nonexistent.  Among the 215 patients who received Levomilnacipran ER (40 mg to 120 mg) a clinically-insignificant weight reduction of ~1.98 lbs. (0.9 kg) was reported.  This study supports the idea that Levomilnacipran is unlikely to cause significant weight change.

2014: A Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Levomilnacipran ER 40-120mg/day for Prevention of Relapse in Patients with Major Depressive Disorder.

Shiovitz et al. organized a 24-week Phase III randomized controlled trial in which the effect of Levomilnacipran ER (40 mg to 120 mg) was compared to a placebo – in 348 patients with major depressive disorder.  Of the 348 participants, 112 received the placebo and 233 received Levomilnacipran ER (40 mg to 120 mg) over a 24-week period.

Researchers tracked body weight changes of participants from baseline (pre-trial) through trial endpoint (24 weeks).  At the trial endpoint, it was noted that Levomilnacipran ER recipients exhibited a slight reduction in body weight of ~1.1 lbs. (0.5 kg) during the double-blind phase – whereas the placebo recipients exhibited a slight increase in body weight of ~1.1 lbs. (0.5 kg).

2013: Safety and Tolerability of Levomilnacipran ER in Major Depressive Disorder: Results from an Open-Label, 48-Week Extension Study.

Mago et al. conducted a 48-week open-label, flexible-dose (40 mg to 120 mg) extension study in which Levomilnacipran was administered to adults with major depressive disorder.  It was mentioned that all participants in this study had previously completed 8 weeks of fixed-dose or flexible-dose treatment with Levomilnacipran ER or placebo – along with a 2-week double-blind taper down period.

Throughout the 48-week open-label trial, researchers tracked: treatment-emergent adverse effects, physical functioning, and laboratory and vital sign measures.  An analysis of the study revealed that 47% of participants completed the full 48-week open-label phase – and that the median treatment length among participants was 40 weeks.

Study authors reported the most common treatment-emergent adverse effects as being headache (22%) and nausea (16%).  Data indicated that Levomilnacipran ER was weight neutral throughout the 48-week treatment period, yielding a slight average body weight reduction of 1.21 lbs. (0.55 kg).

Clinically significant weight gains and losses occurred in 10% and 17% of Levomilnacipran ER recipients, respectively; just one patient (0.1% of participants) discontinued treatment due to weight gain.  Overall, this study supports the idea that Levomilnacipran ER is largely weight neutral – but that it may cause significant weight change in up to 27% of users (with weight loss being more common than weight gain).

2013: Efficacy and safety of levomilnacipran sustained release 40 mg, 80 mg, or 120 mg in major depressive disorder: a phase 3, randomized, double-blind, placebo-controlled study.

Asnis et al. conducted a Phase III randomized, placebo-controlled, double-blind trial to investigate the effectiveness and tolerability of fixed-dose Levomilnacipran SR (sustained-release) versus a placebo in patients with major depressive disorder.  The trial incorporated a 1-week placebo-only phase followed by randomization to receive either: Levomilnacipran SR 40 mg/day (181 patients), 80 mg/day (181 patients), 120 mg/day (183 patients) – or a placebo (179 patients).

Patients remained on either Levomilnacipran SR (at one of the fixed-doses) or the placebo for a total of 8 weeks – followed by a 2-week taper down period.  The most prevalent side effects (occurring in at least 10% of Levomilnacipran SR recipients) included: headache, nausea, constipation, dry mouth, increased heart rate, and sweating; weight gain was not reported.

An analysis of body weight change from baseline among trial participants revealed a slight weight gain among placebo users (~0.41 lbs.) and slight weight losses among fixed-dose Levomilnacipran SR users.  Weight losses among Levomilnacipran SR users were as follows: ~1.1 lbs. (40 mg/day users); ~1.69 lbs. (80 mg/day users); and ~1.65 lbs. (120 mg/day users).

Because the observed weight reductions among Levomilnacipran SR users were very subtle (and not significantly significant), researchers appropriately concluded that Levomilnacipran SR is not associated with clinically-relevant weight change.

2013: Efficacy and safety of levomilnacipran sustained release in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled, proof-of-concept study.

Montgomery et al. investigated the effectiveness and safety of Levomilnacipran SR (sustained-release) with a proof-of-concept study.  Researchers assessed the effect of Levomilnacipran SR (75 mg or 100 mg per day) versus a placebo in adults with major depressive disorder.

For the study, 276 patients were assigned to receive Levomilnacipran SR and 277 patients were assigned to receive the placebo control – for a 10-week period.  A post-hoc analysis revealed that there were no significant differences in weight change (from baseline through trial endpoint) among Levomilnacipran SR and placebo users.

This study further supports the idea that Levomilnacipran SR is unlikely to cause clinically-significant weight change (loss or gain).  Researchers concluded that Levomilnacipran SR is safe, effective, and well-tolerated as an antidepressant.

Note: For additional information about any of the studies discussed below, follow the hyperlink citation included beneath the summaries.

Variables that might influence Fetzima-mediated weight change

There are a host of variables that might influence the amount of weight change that Fetzima users experience.  Such variables might include: length of Fetzima treatment; Fetzima dosage; concurrent substance administration; and individual-specific factors such as genetics, medical conditions, lifestyle, and prior substance use.  Differences in the aforementioned variables likely explains why some Fetzima users experience weight loss – whereas others experience no weight change or weight gain.

  1. Length of Fetzima treatment

The total length of time that you’ve been using Fetzima could influence whether you experience weight change (and its magnitude).  Though research suggests that length of Fetzima treatment is not associated with increased likelihood of weight change as a side effect – it’s possible that a subset of users might report weight change: after a short-term (followed by continued weight change, weight maintenance, OR weight normalization) OR after a long-term (with no apparent weight change over a short-term).

For example, someone who’s only been using Fetzima for a week or two might experience transient weight loss from side effects like hyperhidrosis and appetite loss – each of which might dissipate as the body becomes better-adjusted to Fetzima over a longer-term.  That said, it’s possible that weight loss might emerge over the short-term and persist over a moderate-term until it reaches a peak – followed by weight maintenance over a long-term.

It’s also possible that someone could notice no weight change with Fetzima over a short-term (e.g. the initial month of treatment) followed by weight change over a longer-term of treatment.  Weight change over the long-term could be due to long-term neurophysiologic changes induced by the medication and/or dosage tweaks (e.g. increases).

  1. Fetzima dosage

Research suggests that there don’t appear to be any dose-dependent effects of Fetzima on body weight – such that a 40 mg/day dose is not any more likely to affect body weight than a 120 mg/day dose.  That said, data from some studies suggest a slightly (statistically-insignificant) greater amount of weight loss resulting from doses of Fetzima at 80 mg/day and up.

In a large 8-week trial, weight losses among Fetzima users were: ~1.69 lbs. (80 mg/day); ~1.65 lbs. (120 mg/day); and ~1.1 lbs. (40 mg/day).  Based on the results of this trial, it seems as though using 80 mg/day and above may induce ~0.5 lbs. greater weight reduction (on average) than a lower dose of 40 mg/day.

Because Fetzima induces clinically-insignificant weight loss (likely via noradrenergic mechanisms), perhaps the larger doses bolster the mechanisms by which Fetzima induces weight loss for greater weight loss at higher doses.  Nevertheless, it is important to understand that there may be interindividual variability in terms of how different Fetzima doses affect body weight.

For the average Fetzima user, dosage is unlikely to have a significant influence on likelihood and/or magnitude of medication-induced weight change.  However, for a small percentage of the population, it’s possible that different dosages of Fetzima have different effects on weight.

  1. Concurrent substance administration

If you’re using other substances along with Fetzima such as prescription medications, dietary supplements, over-the-counter medications, illicit drugs, etc. – it’s possible that these could be influencing the weight change that you’ve observed while taking Fetzima.  In fact, it’s possible that concurrently-administered substances might be fully culpable for your weight change – and you might be misattributing your weight change to Fetzima.

Moreover, it’s possible that concurrently-administered substances are enhancing OR counteracting aspects of Fetzima pharmacodynamics in ways that might promote weight gain or weight loss.  For example, administering a noradrenergic medication or psychostimulant with Fetzima might significantly enhance the stimulatory effect of Fetzima to suppress appetite, increase energy (and motivation to exercise), alter hormones, and increased metabolic rate – to induce weight loss.

On the other hand, administering a medication that increases inhibitory activity, increases serotonin reuptake inhibition (and the ratio of serotonin-to-norepinephrine reuptake inhibition), and/or that counteracts the noradrenergic effect of Fetzima – might promote weight gain by increasing appetite, reducing physical energy, modifying hormones, and/or reducing metabolic rate.  Review any substances that you’re using along with Fetzima before concluding that Fetzima is solely culpable for your weight change.

  1. Individual Fetzima user

Many individual-specific factors might influence whether someone experiences weight change on Fetzima – and if weight change occurs, the magnitude of change.  Individual-specific factors that might impact the degree of weight change during Fetzima treatment include: genetics, lifestyle, medical diagnoses, and prior substance use.


The genetics and epigenetic expression of Fetzima users could influence whether weight change occurs as a side effect.  Although the influence of genes and epigenetics on Fetzima-induced weight change remains unclear, it’s possible that genetic differences explain why a small percentage of users report clinically-relevant weight loss OR weight gain.

It is understood that Fetzima is metabolized via the enzyme CYP3A4.  Perhaps differences in CYP3A4 expression (e.g. CYP3A4 poor metabolizers) influence plasma concentrations of Fetzima (relative to dose) and increase OR decrease likelihood of weight change during treatment.  It’s also possible that gene expression could generate unique neurophysiologic responses to Fetzima in ways that might promote weight change in a subset of users.


The lifestyle habits and choices made by Fetzima users could also influence likelihood of weight change during treatment.  For example, someone who diligently regulates calorie intake and physical activity levels to avoid major body weight fluctuations – might not experience any weight change while taking Fetzima.

On the other hand, someone who doesn’t regulate calorie intake and physical activity levels might experience significant body weight fluctuations during treatment due to changes in calorie intake and/or activity – irrespective of the medication’s influence.  Additionally, certain habits like regulating calories, exercising regularly, and managing stress – might prevent weight gain, whereas other habits might promote weight gain.

Medical diagnoses

Preexisting medical diagnoses might influence whether you experience weight change on Fetzima.  For example, someone with rheumatoid arthritis might lose weight while using Fetzima due to unmanaged inflammation and/or medications prescribed to treat the condition.

Conversely, someone with hypothyroidism might gain weight while using Fetzima due to low thyroid hormone production.  If you have any medical conditions besides major depressive disorder and have experienced weight change on Fetzima – evaluate whether those conditions (or medications used for treatment) might explain your weight change.

Previous substance use

Any substances that were discontinued just prior to OR during treatment with Fetzima might account for the weight change that you’re experiencing while using Fetzima.  Hypothetically, let’s assume that you took an antidepressant (e.g. Paxil) before Fetzima that caused you to gain 20 lbs.

Let’s also assume that you completely discontinued Paxil just prior to initiating treatment with Fetzima.  During your Fetzima treatment, you might experience clinically significant weight loss (of ~20 lbs.) due to the fact that the Paxil is out of your system and your physiology is no longer under its influence – enabling you to lose the weight that you gained during Paxil treatment.

However, because you’re taking Fetzima while this weight loss is occurring – you may mistakenly attribute the weight loss as being from Fetzima, when most of the weight loss is probably from discontinuing Paxil – a drug that caused you to gain weight.  Oppositely, if you gain weight while using Fetzima, your weight gain could be due recently quitting a medication that helped you lose weight (and/or maintain a low body weight) – rather than from Fetzima.

Possible strategies to reduce Fetzima-induced weight change

Most Fetzima users are unlikely to experience clinically significant weight change.  If weight change occurs, weight loss seems to be a more common reaction than weight gain.  Nonetheless, if you experience unwanted weight change on Fetzima and want to reverse it – or if you want to decrease the likelihood that you’ll experience weight change on Fetzima, consider implementing the strategies outlined below.  (Prior to testing any of these strategies, verify that they’re safe with a medical doctor).

  1. Use the minimum dose necessary: While the dosage of Fetzima doesn’t appear to influence likelihood of weight change during treatment – it is understood that higher doses alter the neurophysiology of the user to a greater extent than lower doses. This considered, it’s possible that larger doses might enhance weight gain or weight loss – among those who experience these reactions.  To decrease the likelihood of weight change and/or the magnitude of weight change during treatment – consider working with your doctor to find the “minimal effective dose,” or lowest amount needed to treat depression without provoking side effects.
  2. Alter calorie intake: If Fetzima is causing you to gain or lose weight, you may be able to counteract this weight change by modifying your calorie intake.  If you’re gaining a lot of weight during treatment, try gradually reducing your daily calorie intake until you’re no longer gaining weight.  If you’re losing a lot of weight during treatment, try increasing your daily calorie intake until you’re no longer losing weight.
  3. Adjust activity level: If you don’t like tracking your calories and/or tracking calories doesn’t seem to effectively counteract your weight change – consider adjusting your physical activity level or exercise regimen. Engaging in aerobic activity and resistance training can help boost the metabolism to prevent weight gain and improve body composition.  If you’re losing too much weight – try reducing your activity level.  If you’re gaining too much weight – try increasing your activity level.
  4. Discontinue unnecessary agents: As was discussed, sometimes concurrently-administered substances cause weight change that is mistakenly attributed to Fetzima. If you’re using other medications and/or supplements with Fetzima – consider discontinuing all medically-unnecessary agents.  By discontinuing medically-unnecessary, concurrently-administered agents, you might have an easier time maintaining a favorable body weight on Fetzima.
  5. Consider adjunct substances: If you’re using Fetzima as a standalone agent and are dissatisfied with how it’s affecting your body weight, you may want to talk to a medical doctor about using adjunct substances (medications and/or supplements) to modulate your body weight. For example, if you’re gaining too much weight, administering an adjunct substance that’s known to induce weight loss (or prevent weight gain) might be helpful.

Note: In the event that you’re unhappy with the weight change you’ve experienced while using Fetzima, it may be necessary to undergo Fetzima withdrawal and/or transition to another medication.  Always discuss the withdrawal process with a medical doctor before stopping outright.

Have you experienced weight loss or weight gain from Fetzima?

In the event that you’ve used Fetzima and experienced weight loss or weight gain (or no weight change whatsoever) – report this in the comments section below.  Specifically mention how much weight you lost or gained – and how long it took to notice the weight change after initiating treatment.

If you’re a person who lost or gained weight while using Fetzima – what do you think caused the weight change? (Answers might include: appetite change, energy level change, taste changes, metabolism changes, etc.).

From what you’ve observed, was the weight change associated with a significant change in body composition (e.g. changes in fat, muscle, water retention, etc.)?  Do you personally consider the weight change that you experienced on Fetzima to be favorable – or do you hate the way that your weight has shifted while using Fetzima?

To accurately understand your situation, share some details in your comment like: your Fetzima dosage (40 mg to 120 mg); how long you’ve used Fetzima (in total); your age; and your sex (male vs. female).  Do you have any other medical conditions and/or use other substances (medications or supplements) besides Fetzima that might explain your weight change during treatment?

In summary, it is important to understand that most Fetzima users will not experience significant weight change during treatment.  Lastly, if weight change occurs – it’s more likely to be in the form of modest “weight loss” rather than “weight gain.”

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