Last month, September 2023, the FDA approved gepirone hydrochloride for major depression. It should be available to patients in the USA next year.

You may not have heard of gepirone before and it is not licenced for use in the UK. However, it has been to the FDA for approval many times before and rejected, in 2004, 2007, and 2015. There are research papers from 1990 demonstrating the efficacy of gepirone as an antidepressant.

Gepirone is a serotonin 1a partial agonist. It has the typical side effects of dizziness, nausea, insomnia, abdominal pain, and dyspepsia. It is marketed as a novel anti-depressant because of its mechanism of action. It is the first antidepressant that does not have FDA warnings about sexual dysfunction and weight gain.

It is chemically related to buspirone, an oral medication prescribed in the UK for short term treatment of anxiety. Buspirone is a serotonin 1a agonist.

Gepirone is similar to the Selective Serotonin Reuptake Inhibitors (SSRIs), but Gepirone mechanism is slightly different. The partial agonist property offers some flexibility in dosing and mechanism to the best results for individuals.

The approval is for a sustained release preparation as the medication has a short half life (is broken down quickly in the body) so multiple doses a day is needed with the standard release drug. The sustained release drug is also of benefit when reducing and/or stopping gepirone as this is less likely to lead to trough levels of the drug causing symptoms of withdrawal.

The side effect of weight gain is a significant problem with many other antidepressant medications. There are long-term effects of weight gain and obesity that have to be considered if this is a side effect of medication. 

Sexual side effects are often not raised by the patient so doctors often have to ask directly and still may not get a truthful response because of embarrassment. 

We know that side effects and lack of efficacy are major considerations when patients decide to stop their treatment.

We can be optimistic that there is another antidepressant on the horizon. However, there are many treatments of depression, already available in the UK. Moderate to severe depression does not need to be left untreated. Depression is a common and disabling mental disorder that was highlighted by the Royal Colleges of Psychiatrists and General Practitioners in their joint “Beat Depression” campaign from 1992-1996. However, there has been a backlash with allegations of over-treatment that now means that some people do not seek treatment and this can lead to many months of illness, with increasing personal losses (including family, work, home and income) that could be avoided if assessment and appropriate treatment is sought early.