Many people with diabetes take antidepressants, for a variety of reasons. But did you know that these potent pills can affect your glucose metabolism?
This article will cover the common families of antidepressants and the scientific evidence for the effect that they have on blood sugar levels, whether good or bad.
Diabetes and Depression
Diabetes and depression go hand in hand all too often.
Studies show that depression is “more than three times higher in people with type 1 diabetes … and nearly twice as high in people with type 2 diabetes.” It’s not just clinical depression — diabetes is further associated with anxiety, stress, and even the prevalence of eating disorders. Diabetes “distress” is a regular part of life for millions of adults.
All of this anguish can take a serious toll on the metabolism. It doesn’t take a scientific study to realize that diabetes distress and burnout can make it more challenging to manage your blood sugar, and it’s not surprising to learn that such conditions increase the risk of diabetic complications.
Antidepressants are used to treat clinical depression and other mental health conditions, such as obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). They’re also sometimes prescribed for seemingly unrelated conditions, including painful diabetic neuropathy. Many people with diabetes rely on them.
Do Antidepressants Cause Diabetes?
Many studies have found a correlation between antidepressant use and the development of type 2 diabetes, and this association has often been reported by the media.
There is also evidence that pregnant women taking antidepressants are more likely to develop gestational diabetes.
Do antidepressants increase diabetes risks? It’s difficult to say. As a 2013 systematic review notes, people that are using antidepressants may be more prone to developing diabetes in the first place, and “disentangling a drug effect from this complex relationship is challenging.” The authors concluded that it was impossible to establish a causal effect.
To make matters even more complex, we know that some specific antidepressant drugs are associated with blood sugar improvements.
The best review we found of the medical literature was published in the Indian Journal of Pharmaceutical Sciences in 2019. Before we get into the details, here are the authors’ most important takeaways:
- Fluoxetine (Prozac) and escitalopram (Lexapro) may have positive effects on glucose control.
- Paroxetine (Paxil) and fluvoxamine (Luvox) may provoke high blood sugars.
- Duloxetine (Cymbalta) may worsen glucose control.
- Milnacipran (Savella) may “improve metabolic parameters.”
- Mirtazapine (Remeron), which causes weight gain, could increase blood sugar.
Selective Serotonin Reuptake Inhibitors (SSRIs)
SSRIs are the most commonly prescribed antidepressants, partially because they’re believed to cause fewer side effects than competing drugs. The family includes some of the best-known antidepressants on the market:
- fluoxetine (Prozac)
- sertraline (Zoloft)
- citalopram (Celexa)
- escitalopram (Lexapro)
- paroxetine (Paxil)
Some SSRIs probably lower blood sugar, though the effects differ from one drug to another.
A 2022 meta-analysis of 24 studies found that fluoxetine (Prozac) moderately but significantly improved both fasting blood sugar and A1C; it also caused weight loss and improved cholesterol. A 2019 article suggested that fluoxetine might simultaneously improve glucose metabolism and depression “by improving cerebral glucose uptake.”
The effect of sertraline (Zoloft) is less certain. A 2019 study found that the drug lowers A1C, and in rare cases, it has induced hypoglycemia in patients with diabetes. Other studies, such as a 2011 trial, found no glucose-lowering effect. Health authorities such as the UK’s National Health Service warn that taking sertraline may make it more difficult to keep blood sugar stable.
Paroxetine (Paxil) is associated with weight gain, which is usually accompanied by an increase in blood sugar levels rather than a decrease. There is mixed evidence of its effect on blood sugar, with reports that the drug both improves and worsens insulin sensitivity. A wide-ranging 2019 review in the Indian Journal of Pharmaceutical Sciences concluded that paroxetine “might have a side effect on weight gain and metabolic outcomes.”
Citalopram (Celexa) has been linked with lower blood sugar and weight loss.
Fluvoxamine (Luvox) causes hyperglycemia in mice and may do the same in humans (PDF), though the research is less certain.
Finally, escitalopram (Lexapro) has repeatedly demonstrated blood sugar improvements in trials.
Serotonin-Noradrenaline Reuptake Inhibitors (SNRIs)
SNRIs are believed to be more powerful antidepressants than SSRIs, though individual patients vary in their responses. This family includes the following drugs:
- desvenlafaxine (Pristiq)
- duloxetine (Cymbalta)
- milnacipran (Savella)
- venlafaxine (Effexor)
- levomilnacipran (Fetzima)
The evidence for drugs in this family is mixed. For example, some studies have found that duloxetine (Cymbalta) has a modest beneficial effect on glycemia, while others have found the opposite. And an analysis found that venlafaxine (Effexor) has no significant effect on glucose metabolism, at least at normal dosages. Very high doses (or an overdose) of venlafaxine, however, are associated with hypoglycemia, indicating that the drug may have the potential to promote glucose uptake. Desvenlafaxine (Pristiq), likewise, has exhibited both good and bad glycemic effects.
Milnacipran (Savella) may be an exception. Two studies found that the drug has a significant positive metabolic effect, lowering A1C and other metabolic parameters. The positive effects were even found in patients that did not experience any improvement in their depression.
Noradrenaline and Specific Serotonergic Antidepressants (NASSAs)
NASSAs, which are more rarely prescribed, are a good option for people that cannot take more common antidepressants, such as SSRIs. The best-known NASSA on the American market is mirtazapine (Remeron).
The evidence suggests that mirtazapine has confusing metabolic effects. The drug is strongly associated with weight gain, but surprisingly does not seem to prompt the increase in glucose levels that usually accompanies weight gain, and may even improve glucose tolerance.
Tricyclic Antidepressants (TCAs)
TCAs have been around for decades, and have fallen somewhat out of favor because of their side effects. They remain a preferred option for some mental health conditions, such as bipolar disorder, and are also prescribed for painful diabetic neuropathy.
There are many TCAs on the market, including:
- desipramine (Norpramin)
- doxepin (Silenor)
- imipramine (Tofranil)
- nortriptyline (Pamelor)
- protriptyline (Vivactil)
- trimipramine (Surmontil)
One of the side effects of TCAs is weight gain, which is usually accompanied by worsening insulin resistance and elevated blood sugar levels. Studies have also shown that TCAs can “induce hyperglycemia.” These drugs can probably be considered risk factors for elevated blood sugars and the progression of diabetes.
Serotonin Antagonists and Reuptake Inhibitors (SARIs)
SARIs are indicated for depression but are more commonly prescribed off-label for other conditions such as anxiety and insomnia. These drugs are usually considered a backup option in case patients cannot take SSRIs or SNRIs.
The most commonly prescribed SARI is trazodone.
A 2018 study found that trazodone improved the blood sugar levels of about 100 adults with type 2 diabetes. However, the study’s author didn’t believe that the drug itself had a metabolic effect. The blood sugar improvement may have been a result of trazodone’s other positive effects — the patients enjoyed better sleep and less painful neuropathy.
Because trazodone is a sedative, it may be problematic for people with a risk of hypoglycemia — you wouldn’t want your body to be less responsive to a dangerous overnight blood sugar low.
Some antidepressants can affect blood sugar levels, for better or for worse. In many cases, these changes may be mostly related to changes in body weight. These effects are likely to be subtle, but when it comes to diabetes management, every little bit can feel significant.
Mental health issues are extremely common in people with diabetes, and experts agree that addressing depression and related problems should be a priority for patients. It’s not easy to manage your condition if you’re mentally struggling. Diabetes Daily maintains a list of mental health resources.
If you suspect that your antidepressant medication has a negative effect on your metabolism, please discuss your concerns with your healthcare provider.