Antidepressants & Weight Gain; I'm Taking Back Control Over My Body

By: Dr. Nicole Roberts, ND


Weight gain experienced as a result of pharmaceutical prescriptions (that were prescribed in the first place to make us feel better) is be one of the most painful yet disregarded concerns for the millions of patients using antidepressant medications. 


To be told that you are simply “eating too much and moving too little” or that “weight gain is just an unavoidable side effect of treating depression / anxiety” when you know deep down that your metabolism and body’s biochemistry has changed resulting in 10 - 100 lbs of excess weight since you began your medication, is both demoralizing and destabilizing. 


The majority of antidepressant medication scripts are written for women. In 2011, a study reported that 1 in 4 women had been written a prescription for medication for the treatment of mental health, compared to just 15% of men. 


We also know that women are highly scrutinized for the way their body looks. Yes, there are movements that are working to change the social dialogue about this, but for now, both external and internal pressures are at work, contributing to shame, anxiety, avoidance behaviours and worsening depression associated with medication-induced weight gain.  Roots around weight go deep. Ask any woman. Ask any person, really. 


That said, gaining weight is NOT just a socially created cosmetic concern that we need to learn to dissociate from caring about. 

Gaining weight, particularly at the hands of a prescribed medication, feels like our control over our own body has been ripped from us. Not only are we fighting for our mental health, fighting to feel stable, or to feel anything at all, but now we are visibly seeing our physical health unravel in front of us, often whilst being told the two aren’t connected or while being blamed for our own weight changes.



Weight gain as a result of antidepressant medication is not well understood by the medical / scientific community. 

We know that weight gain as a side effect is more likely with certain medications like amitriptyline & mirtazapine and less likely with other prescriptions such as fluoxetine & bupropion. However, patients on medications that are less likely to cause weight gain according to research, can still see substantial changes in their weight, especially if their course of antidepressants is not a short term prescription. Hearing that your recent 50 lb weight gain can't possibly be due to your medication, despite the prescription being the only major change to your lifestyle, because the research doesn't show that effect, is a really alienating statement to be served with. 


We do see a variety of symptoms that are associated with antidepressant use that play a contributory role in weight gain. These symptoms overlap highly with symptoms of unmedicated depression and anxiety as well.

  • Uncontrollable cravings for carbohydrates
  • A lack of motivation to exercise or move at all
  • Deep fatigue
  • Poor sleep associated with low energy and food cravings


The pathophysiological mechanisms for weight gain with antidepressant and antipsychotic medications are still being explored. The balance and regulation of body weight is a complex process controlled by many factors, but our insights into the changing biochemistry of weight with medication use is a growing field of research. Below are a few of the mechanisms associated with medication-induced weight gain


Mechanisms of Medication-Induced Weight Gain at the Cellular Level 

  • Antihistaminergic effects: Drugs with antihistamine effects (blocking the histamine receptors), including prescriptions used in mental health, have long been associated with weight gain, as histamine reduces appetite. 
  • Changes to AMPK (Adenosine monophosphate-activated protein kinase); This little enzyme is know as the “fuel gauge” of the cell and its activation plays a role in metabolism / fat burning and prevention of chronic health concerns like atherosclerosis and diabetes.
  • Hormonal modulation of Ghrelin & Leptin: Leptin, made by fat cells, decreases appetite, while ghrelin, increases appetite. Leptin-resistance, that is, resistance built to the appetite suppressing effects of leptin, is something we are seeing clinically. 
  • Changes to Cytokine Regulation

    TNF-a: This very interesting cytokine has a complex role in body weight regulation. A mediator of inflammation (and the target of certain autoimmune therapies), TNF-a has been shown to play a role in the loss of body fat (hence why a side effect of potent anti-TNF-a meds like adalimumab, is significant weight gain). However, high levels of TNF-a are found in obesity and in this case are instrumental in insulin - resistance, a condition when the body cannot transport glucose effectively (seen in type II diabetes and the weight changes associated with it). 

    Adiponectin: This hormone released from fat cells has anti-inflammatory & protective effects, unlike many other adipokines (hormones released from adipose tissue). However, it is found to be higher in leaner people and greatly depleted in obesity and weight gain. 

  • Melanocortin 4 receptor: The MC4R was the first gene identified as necessary for gastric bypass procedures to effectively cause weight loss. Without signalling of this gene, even surgical procedures to support weight loss could be less effective. Understanding that our DNA expression is a key component of weight management is essential to treating patients with medication-induced weight gain. 
  • Serotonin 2C Receptor: Variants of this specific gene have been implicated in weight gain associated with antipsychotic medication prescriptions. This is a window into the important ideas that our genetics play a big role in how we respond to the medications prescribed to us. 
  • Neuropeptide Y: Neuropeptide Y is a highly abundant peptide in the brain. It is involved in regulating our feeding (eating) behaviour, sexual function, anxiety response, sleep rhythms and more. This little protein governs a whole lot of what we do and how we feel and has been shown to be affected by certain medications. 
  • Canabinoid receptor 1: This gene expressed in the hypothalamic region of the brain, is associated with appetite and satiety (perhaps you could guess this from the name!). Polymorphisms (that is, genetic variation of a gene in the population) are also implicated in medication induced weight gain along with Serotonin 2C , Melanocortin 4 and more. 
  • Muscarinic M3 Receptor Block: Acetylcholine, one of the major neurotransmitters, binds to muscarinic recptors, triggering insulin release in the pancreas. The M3 subtype of the muscarinic rector family plays a key role in glucose metabolism, and thus weight regulation. 


As you can see, weight regulation is complicated at the cellular level as this list is by no means exhaustive. The key with healing metabolism to to affect all of these biochemical systems with simple, lifestyle based treatment plans. This is why naturopathic medicine is such an effective medical model for chronic disease; wholistic natural interventions affect a wide range of biochemical signalling mechanisms to influence positive change across the body. 


Mechanisms of Medication-Induced Weight Gain at the Systems Level

  • Change in Gut Flora: Our gut flora is intricately linked to our brain health and our weight. One of the first drugs used to treat depression was iproniazid, primarily used in the treatment of tuberculosis. Iproniazid has antimicrobial effects. A study in 2017 concluded that antimicrobials are neuroprotective and have an antidepressant effect.(2)  Some antidepressant medications may exhibit some antimicrobial effects and this may account for their ability to reduce depressive symptoms. Other antidepressant medications may further contribute to gut dysbiosis (unhealthy gut flora ratios), feeling the rationale behind why some drugs fail to be efficacious in certain patients. 

Gut flora itself is highly influential when it comes to our weight. Through communication with our brain and metabolism, while being a hot spot for inflammatory processes, the gut is the true foundation of a healthy weight.  Specific strains of probiotics have been found to contribute to substantial weight loss. Clinical occurrences of weight loss following antibiotic therapies or fecal transplants are extreme, but illuminating instances of gut flora affecting weight regulation. 

Overall the gut-brain, gut-weight links are highly integrative and as such, are poised to be the future of lifestyle-based, natural therapies.  

  • Thyroid: Certain antidepressant medications and psychotropic medications have thyroid-toxic effects. By blocking or binding iodine uptake and the essential hormone thyroid perioxidase, these drugs reduce the ability of the thyroid to make functional thyroid hormones.(3) Interfering with the hypothalamic-pituitary-thyroid axis via serotonergic / noradrenergic input and in the case of some drugs, playing a role in autoimmune hypothyroidism, are 2 further ways that medications can inhibit thyroid function and slow the metabolism, causing weight gain, hair loss & fatigue.(3)

Side note: What I am left here thinking, is that if we know gut health & thyroid health contributes to mental health outcomes significantly, and that both may be affected by antidepressants or psychotropic medication, why is it not the gold standard of treatment to refer mental health patients to a naturopathic doctor for concurrent gut, endocrine & dietary care? 


The bottom line is, medications used in the treatment of mental health concerns CAN cause weight gain. This is not always discussed enough when these medications are first prescribed, and too often derided as a valid concern of patients that experience this symptom. 

That said, the potential for weight gain is not a side effect set in stone. There is a lot that can be done before, during and after a patient is on antidepressant or other psychotropic medications, to maintain or work towards a healthy metabolism and a healthy weight. 

This is where a trained naturopathic doctor can be the missing link: 

Moving from feeling trapped with a mental health diagnosis & on a medication that is not making the body feel well, towards a future where your weight, mood, energy and overall health is supported from the inside —> out, is the key role we play as health care providers in the care of chronic mental health concerns. 

A naturopathic doctor with a focus on treating mental health concerns and antidepressant side effects may create an individualized treatment plan for you around the following treatment goals: 

  1. Thyroid monitoring & nutritional thyroid treatments
  2. Gut rehabilitation and healing
  3. Hormone balancing; Read more about the effects of hormones on our mental health: Estrogen Dominance & High Functioning Anxiety 
  4. Metabolic and mitochondrial support at the cellular level using botanical & nutritional supplementation
  5. Supporting healthy, deep, hormone healing, restorative sleep
  6. Diet and lifestyle support of a healthy mood and weight; Managing carbohydrate cravings with simple diet changes 
  7. Integrative management of your case and communication with your medical doctor about weaning off of medication when deemed appropriate by you and your prescribing professional 


The bottom line is, you should always have access to all the necessary information to make empowered choices about your mental health care, including management of side effects and access to medically trained health care providers that know how to treat the body as a whole.

This is the new standard in the changing western medical model of health care. 



1. Himmerich, H, Minkwitz, J, Kirby KC. Weight Gain and Metabolic Changes During Treatment with Antipsychotics and Antidepressants. Endo, Metab & Imm Disord - Drug Targets. 2015 15;4. DOI : 10.2174/1871530315666150623092031

2. Macedo, D et al. Antidepressants, antimicrobials or both? Gut microbiota dysbiosis in depression and possible implications of the antimicrobial effects of antidepressant drugs for antidepressant effectiveness. J Affect Disord. 2017 15;208:22-32. DOI: 10.1016/j.jad.2016.09.012.

3. Sauvage MF, et al. Relationship between psychotropic drugs and thyroid function: a review. Toxicol Appl Pharmacol. 1998 149;2:127-35. DOI: 10.1006/taap.1998.8367