Tesofensine And Antidepressants (Zoloft, Prozac and Wellbutrin)

Tesofensine and antidepressants share a common mechanism of action, as they both influence serotonin, dopamine, and norepinephrine neurotransmitters in the brain. Tesofensine is still an investigational-stage drug with little evidence for its antidepressant properties and interactions with antidepressants. This article covers the plausible antidepressant effects of tesofensine and whether tesofensine interacts with antidepressants at a pharmacological level.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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Tesofensine: Is Tesofensine An Antidepressant?

Tesofensine is a monoamine reuptake inhibitor potentially being developed to treat obesity [1]. It is still under investigation, meaning it is not FDA-approved for treating obesity. In current investigations, Tesomet, a combination of tesofensine with metoprolol by Saniona pharmaceutical company, can reduce some of the side effects of pure tesofensine [2].

Tesofensine works by blocking the reuptake of three neurotransmitters: dopamine, norepinephrine, and serotonin, which is similar to what antidepressants do. By inhibiting the reuptake of these neurotransmitters, tesofensine enhances their neurotransmission, which is thought to contribute to its weight loss effects [3].

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Tesofensine was initially developed for the treatment of neurodegenerative conditions. However, it was observed that individuals treated with the tesofensine experienced unintended weight loss. This led to the investigation of tesofensine as a potential treatment for obesity.

In clinical trials, tesofensine has been associated with dose-related reductions in body weight, body fat, and waist circumference. It has also been observed to improve other obesity-related endocrine factors. The drug has been associated with minor adverse events, including dose-dependent elevations in heart rate and significant increases in blood pressure at the highest dose tested [1].

In addition to its effects on weight loss, tesofensine has been found to have a pronounced effect on appetite sensations, leading to higher ratings of satiety and fullness and lower prospective food intake than placebo. It also has a slight effect on energy expenditure at night, which can contribute to its weight-reducing effect [3].

Uses Of Tesofensine

In clinical trials, tesofensine has shown promising results in reducing body weight, body fat, and waist circumference in obese individuals. It has also been associated with improving obesity-related endocrine factors [1].

Prior to identifying tesofensine’s potential use in obesity treatment, it was studied for its effects on neurodegenerative conditions such as Parkinson's disease. The results were not significantly better on tesofensine as opposed to placebo, but there was a higher rate of adverse events. Due to this, tesofensine was not approved for the management of neurodegenerative conditions [4].

Tesofensine And Antidepressants

Is Tesofensine An Antidepressant?

Tesofensine could also have antidepressant properties. This is because it has been found to increase the expression of specific genes in the hippocampus, such as BDNF, which is linked to the effects of antidepressants like Zoloft or fluoxetine and critically, ketamine [5, 6]. Indeed, reducing reuptake of serotonin, norepinephrine, and dopamine is a common mechanism of antidepressant drugs, which supports the use of tesofensine as a triple-reuptake inhibitor antidepressant [7].

Despite its promising pharmacology as an antidepressant, no studies have been conducted on it in the past 10 years. Therefore, there is not enough evidence to support its antidepressant effects.

Can You Combine Tesofensine and Antidepressants?

To date, there is no direct evidence from the published studies that tesofensine can or cannot be combined with antidepressants. Therefore, to answer this question, we must critically examine the pharmacological effects of antidepressants and tesofensine separately.

Antidepressants are commonly combined with benzodiazepines to relieve anxiety [8, 9, 10], a drug combination which is considered safe. Indeed, this therapy is more effective in the early stages of taking antidepressants than later on in treatment [9].

Combining different types of antidepressants is also fairly common, especially as combination therapy for treatment-resistant patients. For example, selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly combined with a dissimilar antidepressant, such as bupropion (Wellbutrin) or mirtazapine [11].

Indeed, Wellbutrin's effects are very similar to those of tesofensine, as it also inhibits the reuptake of monoamines like dopamine and norepinephrine. Theoretically, combining tesfonensine with antidepressants like SSRIs and SNRIs could have an additive effect on antidepressant response.

A critical difference between tesofensine and Wellbutrin, however, is that tesofensine also blocks serotonin reuptake. This increases the risk of serotonin syndrome, a toxic state caused by excess serotonin in the body manifested by shivering, rigidity, and even seizures. This must be considered when combining serotonergic drugs.

Combining tesofensine with dopaminergic antidepressants, such as Wellbutrin, is also risky. This is because excess stimulation of dopamine can be addictive, and you may develop a tolerance for these drugs, reducing their efficacy [12]. Excess norepinephrine stimulation can increase sympathetic tone, blood pressure, heart rate, and common side effects of taking tesofensine [13].

Therefore, the combination of tesofensine with any antidepressant should be approached with caution until more research is conducted.

Summary: Tesofensine And Antidepressants

To summarise, tesofensine has similar pharmacological effects to antidepressants, but there are no studies directly demonstrating the antidepressant properties of tesofensine. There is also insufficient evidence to indicate whether tesofensine interacts with antidepressants. The most significant risk is serotonin syndrome when combined with serotonergic antidepressants like Zoloft and Prozac and tolerance when combined with dopaminergic antidepressants like Wellbutrin.

Critically, tesofensine is still under investigation and cannot be prescribed. If it is approved, notify your healthcare provider of all current medication so that they can assess whether tesofensine would be suitable for you.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.