• Psychiatric Medications Make Weight Loss Nearly Impossible, but Weight Gain A Snap

    By Rachel Gray

    Who here has trouble losing weight? Why I could not lose the weight baffled me. Well, it’s actually more complex than I thought. First, a lack of self-control is usually the knee-jerk assumption as to why you gain weight. This is based on the belief that weight loss is a simple matter of thermodynamics: one takes in more calories than one “burns”. That is true – but only to a point. I take a combination of psychiatric medications; the resulting weight gain is what the scientific literature calls “antipsychotic induced weight gain” (AIWG) (Lett et al., 2012, P. 242). Knowing mine is AIWG is frustrating: It is why my 900 calorie diet and exercise regimen do not work.

    Proof that most psychiatric medications cause weight gain is well-established (Allsion et al., 1999). ‘Antipsychotic medications’ (interchangable here with the phrase ‘psychiatric medications’) cause “…substantial weight gain, and weight gain is a leading factor in patient noncompliance and poses significant risk of diabetes, lipid abnormalities (that is, metabolic syndrome), and cardiovascular events including sudden death (Lett et al., 2012, P. 242).” The specific medications I’m talking about (and their corresponding illnesses) include the categories of antipsychotics, antidepressants, and mood stabilizers. The illnesses these work on are schizophrenia, depression, and bipolar disorder. What I am not going to address here include the anxiety and attention deficit disorders, and their corresponding medications (which often overlap, but not always).

    Weight gain is THE inevitable side effect of specific psychiatric medications and/or combinations of medications. The comprehensive lay website CrazyMeds (highly recommended: well-researched and consumer-driven) devotes a section about weight gain from psychiatric medications:

    4.1  Weight gain

    There are three known reasons as to why some meds make you fat.

    1. H1 Antihistamines. This is most common way a drug can fatten you up like a veal calf. Most APs, especially Zyprexa are strong-to-potent antihistamines and, as I wrote above, antihistamines make you hungry and encourage you to keep the weight on. Being a potent antihistamine is also why you take these meds as they help you sleep and help fight anxiety. TCAs, especially Remeron, are also strong-to-potent antihistamines and notorious for weight gain.

    2. Serotonin 5HT2C Antagonists. Drugs that interfere with serotonin at this specific receptor at going to make you gain weight. As with antihistamines these meds will make you hungry and keep the weight on. This is the primary reason why second-generation APs, especially Zyprexa and Seroquel, will cause you to pack on the pounds. Additionally they will mess with your insulin resistance, which is why your risk for diabetes increases if you take Geodon or Abilify and don’t gain any weight. And just like antihistamines you take these meds because they are 5HT2C antagonists, as that helps regulate dopamine. Other 5HT2C antagonists include Remeron and Prozac.

    3. Decreasing corticotropin-releasing factor (CRF). Unlike the above two, this one is somewhat obscure, in the world of psychopharmacology at any rate. Like the other two it is possibly why the meds LithiumDepakoteSSRIsSNRIs, and assorted APs and other antidepressants (ADs) work.”

    Health Behaviors

    The typical reaction is to blame excess body fat on the person carrying it. Health professionals I deal with proselytize self-restraint and regular exercise. These are ‘health behaviors’ – control over eating is the biggie to be faced off in this essay because self-control is not as simple as “put down the fork and walk away”. While the exact mechanisms of action for antidepressants, antipsychotics, and mood stabilizers are relatively unknown, the results of Karen Davison’s (2013) study suggested that certain combinations impact weight gain as well as eating habits (more on eating behaviors later) (Davison, 2013, P. 189). Davison’s study (2013) found that there were “significant interactions among antidepressants, …antipsychotics, and mood stabilizers with BMI (P. 188).” Another study found that psychiatric medications, in certain combinations, affect the andrenergic system (having to do with adrenaline, epinephrine, and norepinephrine), although the role of adrenergic receptors in AIWG is unclear  (Lett 2012, P. 255). This all has to do with eating behaviors.

    Why so hungry all the time?

    Psychiatric drugs stimulate one’s appetite so one is hungry all the time (hyperphagia), and therefore one eats more (Davison, 2013, P. 187). Treatment with antipsychotics leads to weight gain and alterations in carbohydrate and lipid metabolisms through increased appetite; leptin and ghrelin play an important role in the regulation of food intake. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Both originate in the periphery (peripheral nerves connect the spinal cord with your limbs) and signal through different pathways to the brain, particularly to the hypothalamus (Esen-Danaci et al., 2008, P. 1434).  This is important because leptin is a protein that plays a major role in the regulation of appetite (‘health behavior’ territory), adiposity (body fat), and body weight. Psychiatric medications stimulate production of leptin and ghrelin.

    After leptin is released by the adipose tissue into the bloodstream, it crosses the blood-brain barrier and binds to the hypothalamic leptin receptors, in the arcuate nucleus, giving information about the body energy stores. Administration of leptin into the arcuate nucleus results in decreased food consumption while leptin deficiency leads to increased food intake (Haupt et al., 2005). Leptin plays a significant role in long-term regulation of energy balance. It also plays a role in short-term regulation of food intake and body weight. Leptin is produced not only by adipose tissue, but also a small amount in the stomach. It plays a role in the control of meal size in cooperation with other satiety peptides (Pico et al., 2003, P. 735).

    Ghrelin is a gastrointestinal peptide hormone that is found in the stomach, the gastrointestinal tract, pancreas, ovary, and adrenal cortex. In the brain, ghrelin-producing neurones have been identified in the pituitary and the hypothalamus (Jin et al., 2007, P. 70). Ghrelin plays a role in regulating feeding behavior and energy metabolism in the central nervous system; it is the first hormone found to stimulate appetite and food intake (Esen-Danaci et al., 2008, P. 1435).

    “The concentration of circulating ghrelin is increased under conditions of negative energy balance such as starvation and anorexia nervosa while decreased under those of positive energy balance such as feeding and obesity in other words circulating ghrelin levels correlate inversely with BMI and body fat percentage (Esen-Danasi et al., 2008, P. 1435).”

    What all this means is that psychiatric medications stimulate your appetite all the time. Regulating your “health behaviors” around eating takes phenomenal willpower and self-control because you are always feeling hunger pangs. It is a real battle to not give in to feeling hungry, something not to be taken lightly.

    I’ve been on a 900 calorie, fresh veggie diet for five weeks, and do 45 minutes of aerobics daily. My weight has stabilized at 165# for five weeks. I should be losing weight, right? Well, that’s what’s so frustrating: If I eat less and exercise more, I SHOULD lose weight. This belief I refer to as “thermodynamics”, whereby one “burns” more calories than one ingests. (I refuse to eat any less, because I detest feeling hungry all the time and my body would probably go into starvation mode…)  My weight gain is not thermodynamics: take fewer calories in, and simply ‘burn’ the fat off with exercise, nope! The weight gain started when my doctor prescribed a combination of medications (Effexor, Abilify, and Lamictal).

    The hated side effect of this medication combination is weight gain, and there’s not a blessed thing I can do except go off the medications (which is not an option). So what all this means is that when you take certain combinations of psychiatric medications, the gods of good health behaviors – Diet and Exercise – mock you. Well, they mock me, anyway…

    Why Diet and Exercise are Perhaps Futile

    First of all, some of us (me) come from hearty peasant stock and our ancestors were broad, plump, and fertile as the women Peter Paul Rubens depicted.

    Peter Paul Rubens, "Venus At Her Mirror"
    Peter Paul Rubens, “Venus At Her Mirror”

    Pharmacogenetic studies are finding that genetics also play a part in moderating the degree of weight gain from psychiatric medications (Lett et al., 2012, P. 244). With no medications, it is a chore and a daily conscientious effort to stay slim and at an optimal doctor’s-health-chart weight (at least, it is for me). The majority of atypical antipsychotics are metabolized by phase I cytochrome P450 (CYP450) isoenzymes (Lett et al., 2012, P. 244). (Isoenzymes are enzymes that differ in amino acid sequence but catalyze the same chemical reaction) (http://www.thefreedictionary.com/isoenzyme). Pharmacokinetic studies found that poor CYP450 activity is associated with increased serum levels of antipsychotics that lead to increased weight gain (Lett et al., 2012, P. 244). Genetics plus psychiatric medications will lead to certain weight gain. That weight stays on, no matter how hard you exercise and deny yourself pizza.

    AIWG goes hand in hand with metabolic changes – the kind that makes you unhappy because you out-grew your favorite pants. “Altered energy homeostasis” and “endocrine disturbances (Davison, 2013, P. 187)” are fancy terms for the physiological side effect of weight gain. Additionally, weight gain is a predictor of metabolic syndrome, which includes diabetes, heart problems, and high blood pressure which puts you at risk for stroke, among other things. The mechanisms linking psychiatric medications with the metabolic syndrome include “dysregulation of the hypothalamic-pituitary adrenal (HPA) axis and autonomic nervous system (ANS) via such pathways as an accumulation of “visceral adiposity” or body fat, and impaired insulin sensitivity, as well as serotonergic (serotonin) activity (Davison, 2013, P. 188).” To sum up the science, your metabolism comes to a screeching halt. No amount of dieting or exercise will help fend off that fat.

    What I would recommend instead 

    First, stay on the medications. My own mental illness is severe and my doctor prescribed a combination of medications that work well. If I quit my medications, I would be slim, sexy, and suicidally depressed.

    Second, self-acceptance of the new, bigger body is key. At this point in psychopharmacology, there are no viable options: The medications cause weight gain. So what is there outside of self-acceptance? It is unrealistic to give hope that we MIGHT one day have drugs that both work and do not make us fat. The medical community has certainly accepted it – they have known for ages that such drugs make patients gain inordinate amounts of weight. It is more realistic to just get used to the additional weight and accept the body as it is. If you need a new wardrobe, go for it!

    Third, eat healthy and do the exercise routines you enjoy. Do it for health and for peace of mind. Just because you probably will not lose the weight, does not mean you should neglect healthy living. Also, what’s wrong with having extra weight if your blood pressure is fine and you show no signs of diabetes or other aspects of metabolic syndrome? This goes to the thought process of stigmatization, and how much we stigmatize ourselves and our bodies to start with.

    Overweight is stigmatized, there’s no doubt about that. But then again, so is mental illness. And that’s a whole other article…


    Allison, David B.; Mentore, J.L.; Moonseong, H.; Chandler, L.; Cappelleri, J.C.; Infante, M.C.; and Peter J. Weiden (1999). Antipsychotic-induced weight gain: A comprehensive research synthesis. American Journal of Psychiatry; Vol. 156. Pp. 1686-1696.

    Cigolini, M.; Targher, G.; Bergamo-Andreis, I.A.; Tonoli, M.; Filippi, F.; Muggeo, M.; and G. DeSandre (1996). Moderate alcohol consumption and its relation to visceral fat and plasma androgens in healthy women. International Journal of Obesity. Vol. 20, Pp. 206–212.


    Web Page, “Side Effects”

    Davison, Karen M. (2013). The relationships among psychiatric medications, eating behaviors, and weight. Journal of Eating Behaviors, Vo. 14, Pp. 187-191.

    Esen-Danaci, Aysen; Sarandol, A.; Taneli, Fatma; Yurtsever, Fatma; and Nesrin Ozlen (2008). Progress in Neuro-Psychopharmacology & Biological Psychiatry; Vol. 32, Pp. 1434-1438.

    The Free Dictionary

    Haupt, D.W.; Luber, M.; Melson, A.; Schweiger, J.A.; and J.W. Newcomer, (2005). Plasma leptin and adiposity during antipsychotic treatment of schizophrenia.  Neuropsychopharmacology; Vol. 30, Pp. 184-191.

    Jin, Hua; Meyer, Jonathan M.; Mudaliar, Sundar; and Dilip V. Jeste, (2007). Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin. Schizophrenia Research, Vol. 100, Pp. 70-85.

    Lett, TAP; Wallace, TJM; Chowdhury, NI; Tiwari, AK; Kennedy, JL; and DJ Muller (2012). Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Molecular Psychiatry, Vol. 17, Pp. 242-266.

    Mayo Clinic Online:

    National Institute of Mental Health (NIMH) Online, Links


    Pico, C.; Oliver, P.; Sanchez, J.; and A. Palou, (2003). Gastric leptin: A putative role in the short-term regulation of food intake. British Journal of Nutrition; Vol. 90; Pp. 735-741.



    Rachel Gray

    Rachel Ann Gray is a PhD student studying Health Communication at the University of Albany (SUNY). She worked and raised a family before starting college at age 38. Her bachelor’s degree is in philosophy.

    Category: FeaturedMedicineMental HealthRachel GraySkepticism

  • Article by: Rachel Gray

    • gewisn

      Excellent! Thank You.

    • I had no idea about this. Perhaps as we understand better how these drugs work (and how our brains work), better alternatives can be devised. This is definitely an area where ethics discussion in medicine seems important and overlooked.

    • Someone

      This makes me wonder what is going on. If you are eating a 900 calorie diet (daily, I assume), it is hard to imagine that you are not losing body fat. Your body consumes a certain amount of energy (calories) every day. The energy short fall has to be caught up from somewhere (body tissues, hopefully fat and not muscle). Perhaps your weight remains the same because of water retention. That is a fairly common side effect of many drugs. The ideal test would be to measure body fat percentage with a reliable measuring method. If your body fat percentage is going down, then you ARE losing fat, and the stable weight or weight gain is coming from something else — most likely water retention.

      • Jennifer Cotton

        I am really surprised by this comment…. this entire article goes into great scientific detail about why she isn’t loosing weight… how psych meds work, metabolic changes, genetics even our own negative self talk are key factors… It is not true that less calories and more exercise will result in weight loss for those on medications such as these. I became a vegan, stopped gluten and have completed weeks of juice fasts, walked 3-5 miles a day and did not loose any weight. only water . This is a brutal situation, it is disheartening beyond belief; especially considering that those on these medications are already depressed. I really am sick of people saying eat less, exercise more because; I have been doing this for 7 years and have only seen my weight go up with each new med. BTW people don’t gain 50 pounds of water weight over a few months time. It once again implys that we are gluttons and have no self control. Good luck if you have a debilitating mental health issue and have not been affected my med induced weight gain… but I would say you are in a very small minority.

        • John OBrien

          your body has to get used to them. been playing with weight loss and weight gain about 5 years now and the meds do suck. but i just lost about 60lbs in theclast few months trying to lose another 30-40lbs but I do agree they make you retain water in the stomach my waist should be 38. it is currently 46 even after dropping 60lbs im lucky if i can get to a 42 lol. so yea they do suck. I am on haldol btw 87.5mg/monthly im shot

    • James Toupin

      I was diagnosed with acute anxiety and panic attacks, which lead to depression. I was prescribed Paxil for the depression and anxiety along with Clonazepam and Ativan for the panic attacks. When I was going through the very worst time my doctor prescribed an antipsychotic as well to control the anxiety and panic. I can’t remember the name of it, but it made me put on over 100 pounds in about 6 months. This weight gain caused me to develop high blood pressure for the first time in my life and had other negative effects on my health. After a few years my condition improved and for the sake of my physical health I was weaned off the antipsychotic and within about 8 months I had dropped the weight I gained and a few extra pounds to boot. My blood pressure and other health problems cleared up as I lost the weight. It has been over two years since I went of the drug and I am doing great. I’m not suggesting anyone go off their medication without the consent and monitoring of their doctor, but when you do feel that you may be feeling better mentally, discuss it with your doctor and together decide the best route to take.

    • Pithecanthropus

      This is a very good and stimulating article, Rachel Ann! What a delight to come upon the work of a friend while following links on the web. I have been taking SSRI’s for the past 16 years (Paxil, then Cipralex, now Zoloft) and have experienced the very sort of intractable weight gain you describe. I’m now a good 140 pounds overweight and it IS affecting my health: high blood pressure and bordering on diabetes. It’s good to get some insight into the (possible) biochemistry of the thing, but I need to find something to do about it and, as with yourself, going off my meds is not an option. I already tried that once–never again!

    • josephnew87

      Checkout this absurd trick to drop upto three Dress Sizes in a week http://www.girlyhacks.com/venusfactor

    • Llewelyn Davis

      I have had good results by consuming very few carbs, adequate protein and a relatively high load of good fats (what constitutes a good fat is controversial for no apparent reason) including coconut, olive oil and high-quality butter. After two decades of SSRI (and various other crazy med) use, I had swollen by about 45 lbs. I’ve finally managed to shed about 35 of my unwanted “friends.” A moderately ketogenic diet ramps up catecholamine release, which is part of the puzzle. And resistance training is a must. Still, it is mystifying why you’re not losing any weight at 900 calories per day. I think if you experiment and keep with it, you can find a regimen that works for you!

      • Jenni Watson

        But have you kept it off with no kidney issues?

    • Malenkaya

      900 calories a day is too little. Women need to consume a minimum of 1200 calories a day. You’re putting your body through starvation mode right now, so your body is clinging to every single fat cell it can in self-preservation. If you haven’t seen a nutritionist or dietician yet, do so.

    • Jennifer Cotton

      This was a terrific article…. I think time spent staying out of the hospital for dangerous manic or suicidal behaviors, weight gain is the the most devastating side effect of this condition. I do not recognize how I look, it is always on my mind, creates social withdrawal and even more sadness. Thank you for understanding and taking the time to write this… Maybe the most indepth and understanding article I have read in 8 years on this subject.

    • Mira

      Wow, I needed to read this. I used to be skinny – I used to be able to eat anything and never gain at all. Despite of this I became anorexic (so skinny did not equal happy) and then later on psychotic. I’ve been on so many drugs, none of which seem to work. And I am a good 40 pounds (!!!) above my former “normal” weight. Due to lack of effect and a dangerous side-effect, I’m currently “clean,” off meds. I have also inherited a genetic joint problem that makes typical exercise impossible (due to extreme pain (I’ve been through a rough birth, so not making that up from nowhere)), and so all I do is to try and eat healthy (extreme diets, starvation, regular diets, none of it works, but it does trigger self hatred) and take all the long walks that I can without reaching the point where the pain makes me unable to stand and/or sit.
      Simply making an effort every day to love myself for who I am, love my body for what it is and as it is, seems to be the only option I have left. But it sucks so hard. I feel fat and ugly. More importantly I feel lazy and unworthy of love, because I’ll never show off my ribs again. Ridiculous. Also I’m pretty sure my bad shape and large stomach must be a sign of bad health.

      Also my doctors have been INSISTING that if I was gaining weight then it was a question of food intake. Like, I must be stuffing myself full of cake if I’m unable to be thin, right? Their explanations never seemed satisfying: yours is at least backed up by more than just “that’s how it is” and prejudice.

      Thank you!

    • Osmund Stimmel

      I’ve been overweight for 10 years and tried so many things. Different things work for different people and I was lucky enough to find one that worked for me. I lost 19 pounds in one month without any exercise and it’s been a life changer. I’m a little embarrased to post my before and after photos here but if anyone actually cares to hear what I’ve been doing then I’d be happy to help in any way. Just shoot me an email at oceanflowers82@gmail.com and I’ll show you my before and after photos, and tell you about how things are going for me with the stuff I’ve tried. I wish someone would have helped me out when I was struggling to find a solution so if I can help you then it would make my day

    • Timothy Cole

      Great article. Kind of made me feel angry to read it, because what you said makes so much sense, yet the stigma still remains. I’ve been overweight for about 15 years now because of psych meds, in particular lithium, mirtazipine, and seroquel. Even a doctor said to me, “Oh you just have to do a bit more exercise than most people”. I’ve done that, over and over again. I always reach a brick wall where I just stop losing weight at a certain point, no matter what I do. I’ve belted myself up about it for too long thinking that it’s just a matter of doing more – it brings me to tears here just writing about it. Because I really gave it a red hot go trying to lose weight, but it just doesn’t happen. I just have to accept, like the author says, my body weight as it is. Being on lithium and seroquel was bad enough, but the mirtazipine really made it a whole lot worse. If I could come off that I would.

      • Brooklyn Park

        I take risperdol and I gained about 70 lbs in my first year of taking that trash drug; my weight went from 170 to 240 lbs.I started eating more healthy and drinking more water in the past 2 years while on psych meds and I lost 50 lbs in 2 years.Now I weigh 190 lbs.For me it’s possible to lose weight on these garbage drugs; it just doesn’t happen quickly.It takes years but it eventually happens if you drink only water ,eat smaller portions,eat more healthy,eat 2 times a day and fight like a warrior against the cravings in addition with physical activity.

    • Joseph Pistachio

      Dear Rachel you should look into a high protein low carb diet like a low glycemic diet program and take a spoonful of coconut oil To speed up your metabolism by 48% and go to the Western A Prices Fondation website because people who are mentally ill need to be on a high protein diet and to cut out the junk food . A high Protein diet will keep your hunger at bay and help you with your mental illness .

    • Jenni Watson

      Very informative.
      I’m on similar meds and have PCOS. I’ve lost over 200 pounds and would probably never be able to do a 900 calorie diet. Part of the key is to eat veggies, fruits, grains, and a bit of nuts and seeds. No calorie dense things, no animal foods. I also stopped being a cardio queen and started lifting weights. Workouts take less time and do more for me. You also have to apply progressive resistance. If you’ve been doing the 45 minutes of aerobics for more than about 6 weeks your body has adapted and no longer exerts itself to do it. With cardio, such as aerobics or jogging you have very few options when your body adapts. Eventually your body just wont be phased by it and you’ll be like so many others and do hours of cardio and not move an ounce. With weight lifting there is progressive resistance so as your body adapts you throw a new exertion at it. (More weight, more reps, slow reps, whatever you want.) It increases your resting metabolism and when you’re ninety you’ll still be able to get up and down from the toilet! lol Check out the Stumptuous blog. She has some amazing resources for lady lifters.

    • To me having a psych med cause weight gain and ultimately diabetes makes me more depressed than before I was put on any psych meds. Abilify almost gave me diabetes and I just stopped taking it altogether before it was too late. You get one med for your psych problems and that med causes side effects. So then your doctor puts you on a second med to combat the side effects of the first med, etc. This could potentially go on forever. I had 14 pills to take with breakfast at one point. I really think there has to be a better way to go than the weight gain and all the other side effects that go with the meds we are using now. Stop blaming the patient for overeating in order to self medicate, the weight gain didn’t happen until the psych meds were started. I am just completely frustrated with all of these meds at this point, I would rather cry all day than to take meds that will make me sicker in the long run. Aren’t there any treatments other than just these chemicals that help with depression?

    • Known Coward

      I lost nearly 60 pounds on Geodon.

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    • Seymour Woods

      What if your taking pills that cause lose of appetite?Will you still gain weight?