Propranolol to treat anxiety: Risks outweigh benefits
By Colleen Cowdery, MD; Jimmy Leonard, PharmD, DABAT; David Veith, MD (UW Psychiatry & Behavioral Sciences)
Propranolol, a non-selective beta blocker with significant sodium channel blocking toxicity in overdose, is sometimes prescribed off-label as a treatment for situational anxiety (e.g., stage fright, fear of flying) due to its ability to dampen physical symptoms such as tremor, tachycardia, and sweating. Propranolol does not treat underlying anxiety disorders, only the resulting somatic symptoms, while potentially worsening depressive symptoms. When propranolol is prescribed off-label to treat generalized anxiety, there is a serious risk of severe illness or death from propranolol overdose.
History and Toxicity
Beta blockers were initially developed in the 1960s for the treatment of angina pectoris, with propranolol entering the market in 1965. That same year, propranolol was first suggested as treatment for anxiety after reports of anxiolysis arose in patients being treated for tachycardia in hyperthyroidism. Propranolol is currently available in both immediate-release (10, 20, 40, and 80mg strength tablets) and extended-release (60, 80, 120, and 160mg strength tablets). Propranolol is one of the most dangerous beta blocker drugs in overdose. Overdose has similar risks to other beta-blockers (refractory hypotension and bradycardia) along with toxic effects of sodium channel blockade, which include QRS prolongation, ventricular dysrhythmias, and seizures. These symptoms are best described in patients who ingested large doses (> 1,000 mg of propranolol). Large propranolol overdoses carry high risk of morbidity and mortality. These patients’ symptoms may be refractory to multiple vasoactive/inotropic infusions, cardiac pacing, intravenous lipid emulsion therapies, and extracorporeal membrane oxygenation therapies. In an observational case series of 444 propranolol poisoning patients reported to poison centers, there was a 9.6% fatality rate (far higher than the overall poisoning fatality rate in the US in 2024 of 0.1%).
Does propranolol effectively treat anxiety disorders?
Although propranolol is often prescribed off-label for “anxiety”, there are limited data to support its use. From a psychiatric perspective, propranolol is not thought to meaningfully treat the underlying core pathology of most anxiety disorders, such as generalized anxiety disorder (GAD) panic disorder, or agoraphobia. For this reason, it is not considered a first-line or even second-line agent for treating these anxiety disorders. Additionally, propranolol is not felt to be useful in the treatment of major depressive disorder with anxious distress, which is a subtype of depression listed in the DSM5-TR, and may in fact worsen depression in these patients.
Although its lipophilicity allows propranolol to readily cross the blood brain barrier and block beta-adrenoreceptors in the central nervous system, its primary effect on anxiety symptoms is believed to be a result of its effects in the peripheral nervous system where it can reduce adrenergic symptoms such as tachycardia, tremor, and diaphoresis. For this reason, propranolol may have a narrow role in providing temporary, symptomatic relief in performance anxiety, where situational autonomic symptoms are the primary drivers of distress and impairment (e.g., stage-fright associated with a single, scheduled presentation or performance). In this context, the off-label use of low dose, immediate release propranolol, taken only as needed rather than scheduled, is accepted in psychiatric practice.
However, extrapolating this benefit to other psychiatric disorders, such as GAD, panic disorder, and major depressive disorder with anxious distress, represents a misunderstanding of their underlying psychopathology. Although autonomic arousal symptoms may be present in these disorders, they are also characterized by maladaptive cognitive patterns such as catastrophizing, intolerance of uncertainty, and overgeneralizations, along with behavioral avoidance. Propranolol does not address these domains, and studies have not demonstrated sustained nor robust benefit for beta blockers in these conditions. For these reasons, psychiatric guidelines do not recommend propranolol for the treatment of these disorders.
In clinical practice, psychiatrists often view scheduled propranolol for anxiety disorders or major depression with anxious distress with skepticism. Concerns about the use of propranolol include the limited data supporting its use, the potential of masking symptoms without actually treating the underlying psychopathology, the potential of worsening depressive symptoms (a listed side effect of beta blockers), and the risks involved in overdose. These concerns are amplified in higher risk patients with a history of depression or prior suicide attempts.
Consequences of propranolol poisonings in anxiety patients
Unfortunately, despite the fact that propranolol does not have any proven benefit for the treatment of anxiety disorders and may worsen depressive symptoms, poison center research has found that “anxiety” is a frequently cited prescribing indication in patients who overdose on their own propranolol. In one study, at least 30% of propranolol poisoning cases reported anxiety as the indication for prescription. Of cases with confirmed outcomes in that study, 22% ended in fatality. This is a much higher degree of mortality than is seen in most pharmaceutical poisonings, highlighting propranolol’s especially elevated risk to life in overdose. Sadly, the risk of propranolol overdose is especially elevated in the population of patients who are prescribed propranolol to treat symptoms of anxiety. Multiple studies have shown that patients with any anxiety disorder diagnosis have an increased risk of suicide attempts, independent of their sociodemographic factors or any other mental health disorders. In a national study in the US comprised of more than 34,000 interviews, over 70% of people who reported any history of suicide attempt in their life also had an anxiety disorder diagnosis. The prescription of propranolol to patients with anxiety disorders allows them access to a very dangerous medication in overdose, without offering any proven clinical benefit.
If not propranolol, what does effectively treat anxiety disorders?
First line treatment for these disorders include psychotherapy, such as cognitive behavioral therapy (CBT), and antidepressant medications, most commonly selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). These interventions are felt to target the cognitive-behavioral and neurobiological components that underpin these psychiatric disorders, and have strong evidence for reducing symptom burden, relapse risk, and functional impairment. Neither of these interventions provide immediate symptomatic relief, and both require patience while they mediate their therapeutic effects. While SSRI and SNRI medications may produce side effects, especially early on in treatment when the medications are being titrated, their longer term risk-benefit profile and relative safety in overdose is far more favorable than the alternatives. Other medications helpful in the treatment of anxiety disorders include buspirone and the short-term use of benzodiazepines in carefully selected patients.
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