Old Medication, New Use: Can Prazosin Curb Drinking?

It’s such a joy for researchers when findings are replicated from study to study because it means the signal they are seeing in the data might actually be revealing the truth.

Prior research

In 2018, we wrote up data from a small clinical trial that I ran as part of an NIH career development grant in a paper entitled: "A randomized placebo-controlled clinical trial of prazosin for the treatment of alcohol use disorder." We concluded that in a sample of 36 people with alcohol use disorder seeking help to reduce their drinking, a medication called prazosin, prescribed over six weeks, was not effective for reducing alcohol consumption. However, in a sub-group analysis inspired by findings from previous research, we did find that this medication helped people reduce their drinking if they had elevated blood pressure at the outset.

To us, our findings were very exciting, despite our sample being small, because it mimicked results from the aforementioned previous research, which discovered doxazosin, a similar medication, helped people with high blood pressure reduce their drinking too.

In behavioral health research, validation of a finding across multiple samples is, unfortunately, more often the exception rather than the rule. But here, we were hopeful that we were onto something. We hoped the fact that we found similar results for similar medications in different patient groups could indicate we were seeing something real here, not just reporting on a statistical anomaly.

It also made biological sense that this medication would work best in people with higher cardiovascular parameters. Prazosin is an alpha-1-adrenergic receptor antagonist, meaning it reduces blood pressure (albeit only weakly) by blocking noradrenergic signaling, which is what happens during sympathetic nervous system activation, or the “fight or flight response." Many people drink alcohol because it has a soothing effect, and alcohol withdrawal is a state of heightened noradrenergic drive.

Maybe prazosin was alleviating some of the core symptoms triggered by heightened noradrenergic tone—sweating, tremor, nausea, anxiety, worry, stress, insomnia—that made it so hard for some people to stop or cut back, both when they were going through withdrawal, and for months after. Maybe these “some people” were people with over-sensitive sympathetic nervous systems.

There were more reasons it all made sense. Many people with post-traumatic stress disorder (PTSD) also struggle with alcohol overuse. PTSD is associated with heightened nor-adrenergic drive. And many of my colleagues in psychiatry were using prazosin to treat PTSD nightmares and flashbacks.

However, I knew that the sample size in our study and the one that inspired our blood-pressure-based subgroup analysis were small. I still felt far from comfortable recommending prazosin for “first-line” treatment for drinking reduction or relapse prevention for my patients with elevated blood pressure and AUD, given the numerous much larger clinical trials that had shown more definitive benefits for medications like naltrexone, topiramate, acamprosate, disulfiram, as summarized in existing helpful practice guidelines papers. But our findings made us happy nonetheless, and we were hopeful that one-day prazosin might be added to this list.

A new study

Today, I felt a surge of delight when I came upon the recently published study, "A randomized controlled clinical trial of prazosin for alcohol use disorder in active duty soldiers: Predictive effects of elevated cardiovascular parameters," authored by Raskind et al.

In this study of 102 veterans undergoing treatment for AUD, these researchers also found that higher pretreatment cardiovascular measures predicted the beneficial effects of prazosin, just like we had. Although 13 weeks of prazosin significantly reduced drinking compared to placebo across subjects, when they looked at the subgroups with elevated blood pressure and heart rate, the effects were even more robust. In addition to reducing drinking amounts, prazosin also reduced depressive symptoms.

Here was a similar story to the one we had told in our paper. Maybe there was something real here.

Even better, they also cited (and brought to my attention) another recent study that found that people with AUD who had higher blood pressures, heart rates, and alcohol withdrawal severity were more likely to improve on prazosin than those with lower values in those three categories, too.

Now, I thought, here were four clinical trials all of which reached similar conclusions. This actually might be a signal I can believe. Maybe I can start using this in my psychiatric practice with my patients. And maybe I can start being less cynical about science again. (My hope had admittedly waned some while in the trenches of research.) It actually can help us uncover the truth, findings are sometimes replicated, and, most of all, study results have the potential to directly inform clinical practice.

Conclusions

1. Even though the research is still in its early days, I will now be more likely to prescribe prazosin to someone with AUD seeking help for their drinking, especially if they have elevated cardiovascular parameters, and if they’ve previously tried and failed at least one of the more standard relapse prevention medications (meaning that the medication didn’t help or caused side effects). Prazosin is relatively inexpensive (it’s generic), fairly safe (there’s nothing reinforcing or addictive about it; it’s been around for decades), and generally tolerable especially in those without low blood pressures (as long as the dose is titrated up slowly because it can cause light-headedness via its effect on blood pressure).
2. More research is needed on prazosin for addictive disorders. We need to continue to study its role in reducing alcohol consumption, but we also need to see if it can help people reduce or stop using other substances—such as opioids or sedative-hypnotics like benzodiazepines—which clearly impact the nor-adrenergic system in a similar manner as alcohol.