Does Phentermine Really Cause Depression?

by Ahmed Zayed, MD on May 13, 2024
Last updated on May 13, 2024

As more people grapple with shedding extra weight, Phentermine becomes a shining star in their journey. This prescription-only ally initiates countless quests toward slimming down. True, it’s not without its flaws – side effects vary from slight annoyances to major challenges. A concern voiced by some is its potential to deepen feelings of sadness. But does it truly drag you into a low mood? Keep reading to uncover the facts.

depressed woman sitting on the bed, holding a mug

Can phentermine cause depression?

Phentermine, sold under brand name Adipex-P, is associated with various side effects of which some are more common than others. Some of the most common adverse reactions of phentermine are a bad taste in mouth, constipation, diarrhea, dry mouth, vomiting, and headache. On the other hand, more serious complications include valvular heart disease, hypertension, insomnia, erectile dysfunction, just to name a few. Depression is not on the list of side effects and complications associated with the use of this drug (1, 2, 3), but the relationship between the two is complicated, and we can’t rule it out.

Evidence of this subject is limited which is why it is crucial to carry out further research. Studies focusing specifically on phentermine and depression could show whether the drug can really contribute to this prevalent mental health problem. Current studies show contradicting findings.

For example, Gadde et al. carried out a study whose primary objective was to assess the efficacy and safety of two doses of phentermine plus topiramate controlled-release combination as an adjunct to diet and lifestyle modification for weight loss compared to placebo.

The study involved 2487 patients of whom 994 were assigned to the placebo group while other groups received a combination of phentermine and topiramate in different dosages. Results showed that phentermine was effective in helping obese patients lose weight, but it also brought some side effects. Besides common side effects such as dry mouth, the drug also induced more serious effects including depression-related adverse events and anxiety-related adverse events.

A different study, published in the Obesity journal, also evaluated the effects of phentermine on weight loss but also assessed the risk of side effects. Allison et al. found that participants who used phentermine lost weight successfully, but some adverse reactions also occurred. Less frequent adverse events included depression, irritability, anxiety, disturbance in attention, among others. While depression was in the group of uncommon side effects, some subjects still experienced it.

Journal Clinical Psychopharmacology and Neuroscience published a review of current evidence on the relationship between phentermine and affective disorders. The paper states that Adipex-P can cause both euphoria and dysphoria as phentermine can affect the mood. That being said, their search for evidence on this specific subject only yielded two studies and four case reports. Scientists agree that’s just not enough to draw any solid conclusion on the topic. After reviewing all trials and studies they found, researchers outlined three potential explanations on the effects of phentermine:

  • Phentermine has the pro-depressive effect that affects a specific subgroup of patients
  • Phentermine has a pro-depressive effect, and it is dose-dependent
  • Phentermine is not associated with depression, and depressive symptoms were caused by topiramate (don’t forget that most studies included a combination of phentermine and topiramate)

How does phentermine cause depression?

Considering the fact that evidence on this topic is limited underlying mechanisms are not fully elucidated. That being said, various theories could explain why phentermine causes depression in some obese patients who take it to lose weight.

Over-stimulates neurotransmitters

A common theory that could explain how phentermine induces depressive symptoms is through the manner it interacts with neurotransmitters in a person’s brain. Basically, the drug over-stimulates neurotransmitters which can lead to effects such as euphoria in some people and depression in others.

Enhanced emotional reactions

As you’re already aware phentermine is a stimulant which is why it can contribute to potentially severe emotional reactions. Stimulants have the ability to amplify reactions and intensify feelings such as anger, sadness, and depression. Basically, they enhance or heighten emotions you already have. For that reason, persons with a history of depression are more likely to experience this side effect of phentermine. Of course, depression due to enhanced emotional reactions may affect men and women who haven’t had this mental health problem before.

Hormonal imbalances

Phentermine is not some random diet pill that everyone can take to lose a few pounds. This is a prescription-only drug that doctors prescribe to certain patients only, usually those with BMI 30 or higher. Your weight has a direct impact on hormone levels. When you gain weight, it changes your hormones, but losing weight does the same. Achieving dramatic weight loss in a relatively short period of time can cause hormonal imbalances due to the fact that estrogen release is connected with the number of fat cells in the body. Hormonal fluctuations have a direct impact on your mood. That’s why some patients may experience low mood, depression, and other negative emotions.

Can phentermine help overcome depression?

Despite the fact that some patients may get depression when using phentermine, others can experience opposite effects. The drug can help some patients overcome depression. Again, multiple mechanisms of action are involved, but studies are needed to elucidate and define them.

One potential theory that could explain why phentermine may help some people overcome depression is that the drug acts like a TAAR1 agonist meaning it binds to and stimulates TAAR1 sites. What does it mean? Stimulation of these particular sites generates the intrasynaptic release of neurotransmitters including norepinephrine, dopamine, and serotonin. These neurotransmitters promote emotional and mental health and wellbeing. In patients with depression, this effect can lead to a better mood. Basically, the same way the drug can cause depression it can also help some people overcome it.

Another potential mechanism of action associated with phentermine and depression management is through the action upon VMAT2 (vesicular monoamine transporter 2) which can also lead to elevated mood improved depression management. Phentermine has a powerful impact on the peripheral nervous system which leads to energy boost, fat burning, and appetite suppression.

Why is this important for depressed individuals? Well, energy boost leads to more exercise and better results from your workouts. Weight loss due to fat burning improves self-esteem while appetite suppression causes calorie restriction which can also improve confidence and mood of an individual. All these things combined promote pleasant feelings which are vital for depression management.

Some people with depression may experience benefits in their mood thanks to improved brain wave modulation. People with certain types of depression exhibit excessive amounts of slow-wave activity and insufficient amounts of fast-wave activity during waking consciousness. However, phentermine-induced modulation of neuroelectrical activity may promote a therapeutic effect in depressed men and women.

Now, we also have to get back to hormonal imbalance. Being overweight or obese disturbs your hormones, and it also contributes to depression and other mental health problems. Weight loss induces changes in your hormones that affect the way you think and behave. While the drastic weight loss may cause hormone imbalances at the beginning, once you start maintaining your weight concentrations of hormones are more balanced which can also promote depression management (4).

Managing depression on phentermine

So, what to do if you’re taking phentermine and experience symptoms of depression? The first thing you need to bear in mind is that you are not powerless. There are various things you can do to feel better while you’re working hard to slim down. Below, you can see some useful tips.

Contact your doctor

While contacting healthcare provider seems such an obvious recommendation it is still largely overlooked. Most people opt not to contact their doctor thinking negative effects of phentermine (or any other drug) would go away on their own. No need to wait for adverse reactions to disappear on their own when you can call and schedule an appointment to see the doctor and learn how to deal with the problem. Your doctor may recommend a different dosage or recommend some measures you can make to feel better.

Seek help and support

Losing weight when you’re overweight or obese can be a stressful endeavor as it is. Now add to that phentermine, and potential risk of depression and things become even more overwhelming. If you have depression while on phentermine there is no need to go through the problem on your own. Seek help and support from your loved ones. Sheer the fact that you’re not alone supports your mental and emotional wellbeing, improves mood, and helps you overcome depression.

Modify your diet

Although phentermine is an effective weight loss pill, it’s still not a miracle drug. Men and women who take phentermine are still required to make some modifications in their lifestyle, i.e., you need to exercise more and change your diet. Instead of junk food which contributes to weight gain and negatively affects your mental health, you need to opt for healthier alternatives that are rich in vitamins, minerals, fiber, enzymes, and other healthy components which also promote mental and emotional health and wellbeing. Plus, well-balanced diet will only improve your weight loss efforts and boost your confidence both of which are important for depression management.

Don’t adjust dosage on your own

If phentermine causes depression, you may feel it’s okay to adjust the dosage on your own hoping to regulate this problem. Make sure you avoid doing that. Your doctor will prescribe the dose that suits your needs the most, and since it’s a prescription medication, you shouldn’t tamper with dosage. Allow the doctor to recommend whether the dosage should be changed or not, avoid doing it on your own.

Manage stress

When stressed out the body produces greater amounts of the hormone cortisol which can aggravate symptoms of depression. Therefore, one of the most important ways to cope with depression is to be active in terms of stress management. Options are endless here as they all come down to your vision of calmness and relaxation. Do something that you find relaxing and turn it into stress-relieving practice that will help you feel better when you feel like you’re stressed out. Improved stress management can decrease the severity of depressive symptoms.


Phentermine is one of the most frequently prescribed drugs for weight loss. Despite its great success in treating obesity, phentermine can induce some potentially serious complications. The relationship between phentermine and depression is complicated, so it’s impossible to say the drug induces this mental health problem for sure, but at the same time, one can’t deny it. More studies are needed to elucidate this subject. Phentermine has an impact on emotional and mental health and wellbeing. In some people, it can aid management of depression. Make sure you discuss this subject with your doctor.


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