Propranolol For Anxiety Disorders: A Nonselective Beta Blocker

Propranolol is a beta blocker originally synthesized in the 1960s by James W. Black, a British scientist.  It is a derivative of older beta-adrenergic antagonists dichloroisoprenaline and pronethalol, each of which lacked safety and efficacy to warrant medicinal usage.  Chemically, propranolol is formed upon insertion of an oxymethylene group into the aryl ethanolamine structure of pronethalol; this increases its overall potency as a nonselective beta-adrenergic inhibitor and mitigates risk of carcinogenicity.

As a pharmaceutical, propranolol is documented as the first ever beta blocker approved for the treatment of hypertension (high blood pressure). In addition to its efficacy as an antihypertensive, propranolol is commonly dispensed by medical professionals as a treatment for conditions including: dysrhythmias, hyperthyroidism, kinetic tremors, and migraine headaches.  Due to its myriad of potential uses, propranolol is classified as an “essential medicine” by the World Health Organization.

Although propranolol has been on the market for over half-a-century (50+ years), it remains underinvestigated as an intervention for neuropsychiatric conditions, particularly anxiety disorders.  That said, it is widely understood that many individuals use propranolol and other beta blockers for anxiety as an “off-label” intervention, especially in situational cases such as performance anxiety and stage fright.  For this reason, those that fail to attain therapeutic anxiolytic benefit from traditional treatments (e.g. SSRIs, benzos, etc.) – may end up considering propranolol as a viable intervention.

How Propranolol May Treat Anxiety Disorders (Mechanism of Action)

To understand how propranolol may alleviate anxiety disorders, it is necessary to investigate its mechanism of action. Pharmacodynamically, propranolol acts as a nonselective beta blocker, thereby inhibiting the effects of epinephrine (adrenaline) and norepinephrine (noradrenaline) at Beta-1 and Beta-2 adrenergic receptors.  Furthermore, propranolol is speculated to inhibit activity of the norepinephrine transporter (NET) and/or stimulate the release of norepinephrine.

In any regard, users of propranolol appear to exhibit increased extracellular concentrations of norepinephrine in certain regions of the brain.  In addition, there is some evidence to suggest that propranolol may act upon serotonin (5-HT) receptor sites such as: 5-HT1B, 5-HT1A, and 5-HT2.  Therefore, it may be necessary to consider that its ability to modulate serotonergic transmission may contribute to its anxiolytic effect.

Beta-1 and Beta-2 receptor blocking:  Propranolol exerts an anxiolytic effect principally by acting as a nonselective beta blocker.  When administered, propranolol binds to beta-1 and beta-2 adrenergic receptors and inhibits activity at the respective receptor sites.  Beta adrenoceptors commonly bind to stimulatory neurotransmitters such as epinephrine and norepinephrine, leading to enhanced sympathetic activation and cardiac stimulation.

Enhancement of cardiac stimulation leads to increases in heart rate, myocardial contractility, and can cause high blood pressure.  Since propranolol inhibits activation of these beta-adrenoceptors, cardiac stimulation and sympathetic activation decrease.  Users are likely to notice decreased blood pressure and a significant reduction in physical symptoms of anxiety.

5-HT receptors: Research suggests that propranolol may exhibit a modest affinity for 5-HT receptors.  Though a majority of propranolol’s anxiolytic effect stems from its nonselective beta-adrenoceptor inhibition, its affect on 5-HT receptors may also reduce anxiety via modulation of serotonergic signaling.  Studies have shown that propranolol affects several 5-HT receptors including: 5-HT1B, 5-HT1A, and 5-HT2 – each of which may contribute its anxiolytic properties. (Source: http://www.ncbi.nlm.nih.gov/pubmed/2539480)

• 5-HT1B agonist: Of all serotonergic receptors, propranolol binds with highest affinity to 5-HT1B sites. Upon binding to 5-HT1B receptors, propranolol acts as an agonist, which in turn facilitates vasoconstriction of blood vessels and reduces vasoactive neuropeptides released by trigeminal nerves.  Clinical research has shown that 5-HT1B selective agonism decreases anxiety in animal models; perhaps something similar occurs in humans.
• 5-HT1A antagonist: Propranolol binds to 5-HT1A receptors with a lower affinity than 5-HT1B. Upon binding to 5-HT1A receptors, propranolol acts as an antagonist, thereby preventing activation of the receptor site.  Studies have shown that individuals with 5-HT1A receptor abnormalities often exhibit symptoms of anxiety.  Antagonism of 5-HT1A receptors is understood to potentiate the therapeutic efficacy of SSRIs and may decrease anxiety.

Catecholamine downregulation: Research suggests that propranolol administration decreases synthesis and uptake of catecholamines (dopamine and norepinephrine) in animal models.  It significantly reduces concentrations of dopamine by inhibiting the effect of tyrosine hydroxylase, an enzyme responsible for converting the amino acid L-tyrosine into L-DOPA, and thereafter, into the neurotransmitter dopamine.  Reduced synthesis and uptake of dopaminergic neurotransmission may contribute to the anxiolytic effect of propranolol.

Propranolol is also thought to decrease concentrations of norepinephrine in various regions of the brain.  Perhaps its ability to downregulate the synthesis and uptake of catecholamines, particularly dopamine, contribute to its anxiolytic effects in some individuals.  Individuals with high anxiety are documented as being sensitive to high dopamine concentrations; reducing excess dopamine may induce relaxation.

Neuroelectrical changes: It is possible that propranolol alters neuroelectrical activity in the brain, possibly contributing to its anxiolytic effect.  Research indicates that propranolol may increase slow brain waves such as alpha and/or theta waves.  A strengthening of the alpha and/or theta band may prove therapeutic for severe anxiety, particularly among those with somatic subtypes in which the strength of alpha/theta are impaired during states of wakefulness.  The shift from excess beta wave activity to an increase in slower waves such as alpha and theta may facilitate relaxation.

Voltage-gated sodium channel blocking: Propranolol is comprised of two enantiomers R-(+)-propranolol and S-(-)-propranolol, each of which block voltage-gated sodium channels within the brain.  The degree to which they block voltage-gated sodium channels is contingent upon the dosage of propranolol administered.  The greater the dosage of propranolol administered, the more substantial the voltage-gated sodium channel blocking.

Its ability to block voltage-gated sodium channels in a dose-dependent manner influences the firing of various neurons.  This in turn may contribute to anxiolytic effects experienced by propranolol users.  That said, the extent to which a blocking of voltage-gated sodium channels contributes to the anxiolytic efficacy of propranolol isn’t elucidated.

Decreased sympathetic activation: Many individuals with anxiety disorders are stuck in a perpetual state of “freeze-fight-or-flight” as a result of an overactive sympathetic nervous system.  This leads to an increase in stimulatory neurotransmitters (e.g. norepinephrine, dopamine, etc.) and hormones (e.g. cortisol).  Studies suggest that propranolol decreases sympathetic activation and is an effective agent for combating sympathetic hyperactivity.

As a result, individuals using propranolol report reductions in physical symptoms of anxiety and stress.  The high blood pressure, muscular contraction, and heart palpitations associated with sympathetic activation – typically decrease after propranolol administration.  Propranolol attenuates the fight-or-flight response in a dose-dependent manner, which in turn minimizes somatic anxiety and may also improve certain psychological aspects of anxiety via decreases in catecholamines.

Propranolol for Anxiety Disorders (Review of Research)

Propranolol emerged as a pharmaceutical in the 1960s and has been subject to significant investigation as an intervention for anxiety.  Below is a synopsis of the research examining the anxiolytic properties of propranolol.  In most studies, researchers suggest that propranolol is a safe, effective treatment for anxiety.  That said, since many studies are small-scale, lack robust designs, and focus on highly-specific subtypes of anxiety – making it difficult to interpret propranolol’s anxiolytic efficacy compared to FDA approved anxiolytics.

2015: Propranolol for the treatment of anxiety disorders: Systematic review and meta-analysis.

A systematic review and meta-analysis by Steenen et al. (2015) investigated the efficacy of propranolol for anxiety disorders.  At the time of writing this article, this report is the most conclusive, up-to-date publication on propranolol as an intervention for anxiety disorders.  Since this is a systematic review, it is considered the most reliable form of evidence for real-world medical application.

It is important to note that prior to this systematic review, no prior reviews nor meta-analyses had been conducted to investigate propranolol as a treatment for anxiety disorders.  To meet inclusion criteria for the review, studies needed to be randomized and controlled.  In other words, they needed to compare the efficacy of propranolol to that of a placebo (or another medication).

Additionally, all included studies focused specifically on the efficacy of propranolol in reducing state or trait anxiety among individuals with anxiety disorders.  Researchers scoured publication databases and were able to dig up a total of 8 studies that met inclusion criteria.  Of these 8 studies included: 4 investigated the efficacy of propranolol for panic disorder (with or without agoraphobia); 2 of propranolol for specific phobias; 1 of propranolol for social phobia; and 1 of propranolol for PTSD.

Upon analysis of the results, researchers concluded that propranolol didn’t differ in efficacy from benzodiazepines for the short-term treatment of panic disorder (with or without agoraphobia).  It was also discovered that propranolol failed to reduce symptomatic severity of PTSD.   Authors concluded that quality evidence is inadequate to justify the administration of propranolol for anxiety disorders.

That said, it is important to realize that this meta-analysis may have been prematurely conducted in that there were few studies that fit inclusion criteria – each of which had limited numbers of participants.  Although propranolol appears ineffective panic disorder, its efficacy was indistinguishable from benzodiazepines.  Since benzodiazepines are considered clinically effective for panic disorder, and they failed to differ in efficacy from propranolol, it is impossible to reflexively dismiss the therapeutic efficacy of propranolol.

What’s more is that although propranolol didn’t reduce symptomatic severity of PTSD, results were interpreted from a single, standalone study with only 19 participants.  This systematic review simply highlights the fact that additional, larger-scale studies are warranted before any definitive conclusions can be made regarding propranolol’s anxiolytic efficacy.  Although this systematic review doesn’t support propranolol as an intervention for anxiety disorders, it shouldn’t be dismissed as a therapeutic option solely based on this report.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/26487439

2012: Oral propranolol–efficacy and comparison of two doses for peri-operative anxiolysis.

A trial conducted by Khadke, Khadke, and Khare (2012) analyzed the efficacy of propranolol as a perioperative anxiolytic.  Researchers understood that individuals undergoing surgery typically experience an increase in anxiety and stress as a result of the surgical procedure.  Although the additional anxiety associated with the surgery isn’t considered life-threatening, it is considered problematic from the perspective of the patient, and often requires additional medical treatment.

As an intervention for perioperative anxiety, researchers speculated that administration of propranolol at 20 mg or 40 mg may prove therapeutic.  They set up a double-blind, randomized study with 60 healthy individuals set to undergo minor surgeries.  The participants were divided into two groups: a control group of 20 individuals receiving no premedication and another group of 40 individuals receiving propranolol as a premedication.

Within the group of 40 individuals receiving propranolol, 20 individuals received 20 mg doses and the remaining 20 individuals received 40 mg doses.  In all 60 participants, anxiety levels were measured and recorded with a 4-point anxiolysis score before and after surgery.  Researchers discovered that individuals receiving propranolol (20 mg or 40 mg) experienced significant reductions in perioperative anxiety.

Authors noted that 20 mg appeared equally as effective as the 40 mg and yielded fewer side effects.  Hence they recommend administration of 20 mg propranolol as a perioperative anxiolytic.  Although perioperative anxiety is a transient form of anxiety, it provides evidence that propranolol is capable of reducing anxiety scores in anxiety-provoking situations such as surgery.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/23520670

2010: Propranolol and D-cycloserine as adjunctive medications in reducing dental fear in sedation practice.

An investigation conducted by Heaton, McNeil, and Milgrom (2010) sought to determine the efficacy of propranolol and d-cycloserine as treatments for decreasing patient fear of dental procedures.  Prior research documented that sedation proved helpful in decreasing fear of dental procedures among patients that needed dental work, but were fearful of visiting the dentist.  Researchers also noted that behavioral interventions as a management strategy for dental fears are considered effective for fear reduction.

Digging through the published literature, researchers discovered that pharmacological interventions such as propranolol and d-cycloserine are viable interventions for reducing dental fears among patients.  Although they acknowledge the fact that additional research is warranted to elucidate the efficacy of propranolol, evidence suggests that it can help patients manage physiological symptoms of anxiety associated with dentistry.  They surmise that propranolol (and other beta-blockers) not only mitigate anxiety over a short-term, but that they could sustain an anxiolytic response over the long-term.

A sustained anxiolytic response among dental patients taking propranolol may occur as a result of its ability to modulate fear-memory consolidation.  Furthermore, propranolol alleviates symptoms of anxiety in dental patients without inducing significant sedation and/or impairing conscious awareness to the same extent as a benzodiazepine.  Although propranolol is not a risk-free intervention, it may be a viable pharmacological attenuator of dental anxiety.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/20151608
• Source: http://www.ncbi.nlm.nih.gov/pubmed/1918581/

2003: Immediate treatment with propranolol decreases posttraumatic stress disorder two months after trauma.

A study published by Vaiva et al. (2003) documented the efficacy of propranolol for the treatment of PTSD when administered after the traumatic experience.  Researchers recruited a total of 19 patients, each of which had been exposed to a traumatic experience.  A total of 11 patients were administered propranolol at 40 mg, three times per day (t.i.d.), for a total of 7 days (1 week).

After the initial week of propranolol treatment, the 11 patients were tapered off propranolol over the course of 8 to 12 days.  The 11 patients were then compared to a group of 8 individuals that participated in the study, but declined the option to receive propranolol treatment.  The two groups (those that received propranolol and those that declined propranolol) were considered similar in terms of demographics, trauma exposure, physical injuries, and emotional responses.

Results from the study indicated that PTSD diagnoses and symptoms were greater among individuals that declined propranolol treatment compared to those that received propranolol 3-times per day for 7 days.  Researchers concluded that propranolol may mitigate symptoms of PTSD, and may (in certain cases), prevent PTSD onset.  Although this study was small-scale, it highlights the anxiolytic efficacy of propranolol, particularly as an immediate intervention for PTSD.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/14573324

2001: Interest of propranolol in the treatment of school refusal anxiety: about three clinical observations.

A publication by Fourneret et al. (2001) discussed three cases in which propranolol was used as a successful intervention among children with “school refusal anxiety.”  School refusal anxiety is a condition characterized by excessive anxious thoughts regarding school, leading children (between the ages of 8 and 13) to refuse attendance.  Many children with school-refusal anxiety struggle to feel comfortable at school, socially and academically – which can have deleterious long-term consequences if left unaddressed.

While cognitive behavioral therapy (CBT) may improve outcomes among children with school refusal anxiety, pharmacologic interventions are necessary to consider.  One viable intervention that has been documented in several cases is propranolol.  Unlike benzodiazepines and antidepressants which may be harmful to a child without a fully developed brain, propranolol is thought to be less risky.

Researchers were able to find 3 distinct cases in which children with school refusal anxiety benefitted from propranolol.  Propranolol administration significantly reduced reintegration and rehabilitation times among children with school refusal anxiety.  Authors noted that since propranolol hasn’t been studied for the treatment of school refusal anxiety in a placebo-controlled, double-blinded, randomized manner – it is difficult to draw conclusions from the case reports.

That said, propranolol appears well-tolerated by children with school refusal anxiety, and preliminary evidence suggests anxiolytic benefit.  This report provides further evidence that propranolol effectively decreases anxiety among children without significant safety concerns.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/11865565

1998: The effect of propranolol versus placebo on resident surgical performance.

A study published by Elman et al. (1998) tested whether propranolol could decrease performance anxiety among surgeons.  Researchers specifically aimed to measure whether propranolol would decrease tremors among surgeons performing ocular (eye) microsurgery without compromising safety of the patient or the surgeon.  Since tremors are indicative of anxiety, a significant reduction in the number of surgical tremors would signify efficacy of propranolol for treating performance anxiety.

A randomized, double-masked, crossover design was employed by researchers over a trial period of 10-weeks.  They recruited a total of 5 ophthalmology residents for the study, giving them either: a placebo or propranolol (40 mg) – one hour before performing a microsurgery.  To minimize safety risks, all participants had been screened prior to the trial with a test dosage of propranolol; none exhibited unwanted side effects.

To measure performance anxiety, all 5 residents, as well as an attending surgeon (observer) graded: overall tremor, amount of tremor during initial few sutures, anticipated surgical difficulty, actual surgical difficulty, and observed anxiety.  The specific type of procedure was recorded, complications were noted, and side effects were documented.  Researchers collected data from 73 surgeries in which propranolol was administered in 40 surgeries; a placebo was administered in the remaining 33 surgeries.

Propranolol significantly reduced anxiety as judged by the resident surgeon, decreased total tremors, as well as decreased tremors during the initial few surgical sutures.  In all cases, no significant side effects nor risks (to surgeon or patient) were observed as a result of propranolol administration.  This trial highlights the efficacy of propranolol (40 mg) for the treatment of performance anxiety among surgeons when administered 1-hour pre-surgery.

Researchers noted that it was unclear as to whether a decrease in tremors and/or anxiety improved surgical performance.  However, this trial provides evidence to support the anxiolytic efficacy of propranolol.  It could be speculated that aspects of surgical performance may have improved as a result of the anxiety reduction and/or inferred that performance anxiety associated with other occupations (e.g. acting) could benefit from propranolol.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/10360293

1993: Propranolol reduces the anxiety associated with day case surgery.

A study conducted by Mealy et al. (1993) investigated whether propranolol could decrease anxiety among 53 patients undergoing day case surgery at University Hospital in Ireland.  The study was considered randomized and placebo-controlled.  The 53 patients scheduled for day case surgery were assigned to randomly receive either propranolol (10 mg) or a placebo on the morning of their surgery.

To gauge how patients were affected by propranolol, researchers documented measures of: blood pressure, pulse, anxiety, pain score, and patient satisfaction.  Results indicated that patients receiving propranolol (10 mg) on the morning of surgery experienced significantly lower Hospital Anxiety and Depression scores compared to the control group (receiving the placebo).  Researchers concluded that low dose propranolol (10 mg) administered on the morning of day case surgeries significantly reduces patient anxiety.

This study provides additional evidence to suggest the efficacy of propranolol as a perioperative anxiolytic.  Anxiety scores among individuals that had received propranolol were significantly reduced compared to those who received the placebo.  Based on these results, one may speculate that propranolol could reduce other forms of situational, transient, or event-specific anxiety.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/8679756

1991: Beta-blocking drugs and anxiety. A proven therapeutic value.

A review published by Laverdure and Boulenger (1991) assessed the therapeutic potential of beta-blockers such as propranolol for the treatment of anxiety disorders.  Authors note that alternative anxiolytics to benzodiazepines may be preferred for several reasons.  Benzodiazepines are associated with psychomotor impairment, dependence, protracted withdrawals, rebound anxiety, and have been linked to dementia.

For this reason, researchers believe that beta blockers such as propranolol are worth exploring as anxiolytics.  Upon analysis of previously published research, authors noted that propranolol was effective for the treatment of anxiety in placebo-controlled studies.  It demonstrated the greatest efficacy for the treatment of anxiety: characterized by somatic symptoms / adrenergic tone, of moderate severity, of recent onset, and that doesn’t fit DSM criteria for a chronic anxiety disorder.

In other words, authors suggest that propranolol may be a viable intervention for cases of performance anxiety, public speaking, or highly-specific social phobias.  Researchers documented that standard therapeutic dosages of propranolol range from 20 mg to 40 mg at varying frequencies of administration (from 1 to 3 times daily).  That said, it was mentioned that the sustained efficacy of propranolol when administered for over 4 weeks, remains unknown.

Authors of this report suggest that beta-blockers, propranolol in particular, should be regarded as viable alternatives to benzodiazepines and antidepressants for the treatment of anxiety.  The long-term outcomes among regular beta-blocker users are unknown.  However, they may prove to be a sustainable, efficacious intervention for specific subtypes of anxiety when used under medical supervision.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/1686251

1991: Effect of a beta-adrenergic blocking agent on dental anxiety.

A study by Liu, Milgrom, and Fiset (1991) analyzed the efficacy of propranolol for the treatment of dental anxiety.  It is understood that many individuals are afraid to seek dental treatment due to dental phobia or fear of the dentist or dental procedures.  Researchers hypothesized that propranolol may alleviate dental anxiety among individuals with dental phobia.

The recruited a total of 23 individuals with dental phobia and set up a double-blind, placebo-controlled study.  Of the 23 participants, 12 received the propranolol (80 mg or 120 mg) and the remaining 11 received a placebo.  Researchers noted significant differences in self-reported anxiety levels at the injection phase of the procedure, decreased overall pain, and lower aversive behavior – among those that had received propranolol (as opposed to the placebo).

It was concluded that beta-adrenergic blockers, particularly propranolol, appear efficacious as perioperative anxiolytics among those with dental phobia.  No major adverse reactions or tolerability issues were reported.  Although this was a small-scale study, it highlights the efficacy of propranolol in attenuating anxiety associated with medical procedures.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/1918581/

1988: Propranolol treatment for childhood posttraumatic stress disorder, acute type. A pilot study.

A study from 1988 documented the effects of propranolol for the treatment of childhood PTSD.  Researchers investigated 11 cases of PTSD stemming from physical abuse, sexual abuse, or a combination of both.  The childhood PTSD manifested symptoms of hyperarousal and excess agitation among the 11 individuals.

A trial that implemented a specific “B-A-B” (off-on-off) design for medication administration was conducted.  Children were each given administered propranolol, a beta-adrenoceptor antagonist (blocker).  Throughout the trial, researchers measured PTSD symptom severity and thereafter, compared severity of symptoms during the “B” (no medication) phases to the “A” phases (propranolol).

Results suggested that symptomatic severity of PTSD significantly decreased while receiving propranolol compared to pre-treatment or post-treatment.  Although this was a small-scale trial without a placebo-controlled, double-blinded, randomized design – it highlights improvement in PTSD severity among those taking propranolol.  This suggests that propranolol may be an effective pharmacologic intervention for ameliorating symptoms of PTSD among children.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/3177336/

1987: Comparative efficacy of propranolol, chlordiazepoxide, and placebo in the treatment of anxiety: a double-blind trial.

Propranolol’s efficacy as an anxiolytic was tested by Meibach et al. (1987) and compared to Librium (chlordiazepoxide).  Researchers set-up a double-blind, placebo-controlled study with 212 patients to be conducted over a 3-week period.  In an initial introductory phase of the trial, all participants received a placebo for one week.

Next, there was a wash-out phase, and thereafter, participants were randomly assigned to receive propranolol (doses of 80 mg, 160 mg, or 320 mg per day), Librium (doses of 30, 45, or 75 mg per day), or a placebo.  Throughout the study, participants were assessed for anxiety with 3 distinct measures including the: Hamilton Rating Scale for Anxiety (HAM-A), Covi Anxiety Scale (CAS), and Clinical Global Impressions scale.  Additional measures were collected based on participant-rated scales including the: Symptoms Checklist 90 and Profile of Mood States (POMS).

After the first week, participants that had received propranolol or Librium experienced significant reductions in anxiety (compared to those that had received the placebo).  Anxiolytic efficacy was evidenced by significant reductions in HAM-A and CAS scores among participants receiving propranolol or Librium.  After the second week, solely propranolol demonstrated anxiolytic efficacy over the placebo as evidenced by lower HAM-A and CAS scores.

Side effects were considered similar among those receiving propranolol and Librium; unlike Librium, propranolol didn’t cause libido changes or fatigue.  However, propranolol was associated with drowsiness and ingestion.  This study provides evidence to support the sustained anxiolytic efficacy of propranolol when administered for consecutive weeks – all without adverse reactions.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/3305488

1986: Propranolol and atenolol in the treatment of anxiety.

A study conducted by Peet and Ali (1986) sought to determine whether propranolol or atenolol were safe and effective treatments for anxiety.  Researchers specifically focused on patients with refractory cases of generalized anxiety that failed to respond to standardized pharmacological treatments as prescribed by a family doctor.  They noted that such refractory cases may require an alternative form of treatment.

Authors of the study noted that propranolol was an effective anxiolytic with a favorable safety profile for the treatment of generalized anxiety.  Another beta-blocker known as “atenolol” was also noted as being effective for treating generalized anxiety.  However, atenolol wasn’t considered a viable treatment due to its propensity to induce adverse cardiovascular effects, especially among those with anxiety.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/3549876

1985: The use of propranolol in the treatment of anxiety disorders.

A report by Fonte and Stevenson (1985) summarized the available research of propranolol as a pharmacological intervention for anxiety disorders. Researchers noted that propranolol was initially studied in 1966 and appears to effectively alleviate somatic symptoms of anxiety.  That said, researchers were unable to elucidate whether propranolol is a universally efficacious option for all types of anxiety disorders.  Authors highlight various drawbacks associated with using propranolol (and beta-blockers) as a neuropsychiatric anxiolytic.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/3894197

1980: Propranolol in chronic anxiety disorders. A controlled study.

A study by Kathol et al. (1980) aimed to determine the usefulness of propranolol as a treatment for chronic anxiety disorders.  Researchers recruited 26 individuals diagnosed with chronic anxiety disorders and set-up a double-blind, crossover study.  Of the 26 participants, it was noted that propranolol significantly reduced anxiety in a total of 17; around ~65% attained anxiolytic benefit.

Observer ratings suggested that somatic and psychic symptoms significantly improved following propranolol administration.  Some side effects such as: dizziness, fatigue, and insomnia resulted from propranolol – but most were considered mild.  Researchers suggested that propranolol elicits a significant anxiolytic effect via the CNS.

This study provided early evidence that propranolol may be of benefit to individuals diagnosed with anxiety disorders.  It is important to note that although it appeared to be an effective intervention in this study, its efficacy as compared to other FDA-approved anxiolytics remains unknown.  It should also be mentioned that this was a small-scale study and lacked a placebo control, possibly affecting results.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/7447618

1976: Oxprenolol and propranolol in anxiety states. A double-blind comparative study.

A study by Becker (1976) was conducted to determine whether the drugs oxprenolol and propranolol could reduce anxiety.  Researchers set up a double-blind study and recruited patients that were known to have anxiety and/or tension.  To gauge anxiolytic efficacy of each drug, participants were administered a 19-item psychiatric rating scale to track symptoms.

Severity of anxiety was also assessed by investigators and participant self-assessments.  Furthermore, tolerance to propranolol was evaluated throughout treatment.  Results indicated that both oxprenolol and propranolol effectively treated anxiety and tension, but oxprenolol exhibited favorable tolerability of the two.

This provides evidence to suggest that propranolol and oxprenolol can effectively treat anxiety and tension among certain individuals.  Despite propranolol’s efficacy, it appears as though other agents such as oxprenolol are better tolerated.  For this reason, it may be necessary to consider that other beta adrenergic blockers besides propranolol may be preferred interventions for anxiety.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/772831

1976: Propranolol in the treatment of anxiety.

A report by Suzman from 1976 discussed propranolol as a treatment for anxiety disorders.  Suzman noted that since 1964, a total of 725 individuals exhibited anxiety disorders and of the 725, a total of 513 were treated with propranolol for time spans ranging from a few days to over 10 years.  Some of these individuals utilized propranolol intermittently, whereas others administered it regularly (e.g. on a daily basis).

It was also reported that of the 513 individuals treated with propranolol, 237 had previously been given psychiatric drugs such as benzodiazepines and/or phenothiazines – each of which failed to provide anxiolytic efficacy and/or provoked adverse effects.  Among each individual receiving propranolol, dosages were adjusted to maximize therapeutic efficacy.  In most cases, dosages between 80 mg and 320 mg per day served as successful anxiolytic interventions.

In a small percentage of cases, daily propranolol dosages were titrated up to 1200 mg to control severe, unremitting symptoms.  Researchers discovered that in a majority of patients receiving propranolol, somatic and psychological symptoms of anxiety significantly improved.  What’s more is that among individuals with comorbid depression, approximately 2/3^rds derived an antidepressant effect from propranolol.

Among the remaining 1/3^rd with unresponsive depression, all cases responded to adjuvant pharmaceutical antidepressants.  Moreover, dosage requirements of propranolol appeared to diminish over time and sustained symptomatic remission was common.  The study author noted that single-blinded, placebo-controlled trials noted the efficacy of beta-blockers for the treatment of anxiety.

In conclusion, the author suggests propranolol is an effective intervention for the treatment of both somatic and psychological anxiety.  Propranolol dosage adjustments are typically necessary in early stages of treatment, however, the side effects appear favorable to older benzodiazepines and tranquilizers.  This study provides strong evidence to suggest propranolol’s efficacy as an anxiolytic.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/787957

1976: Somatic anxiety attacks and propranolol.

A report published in 1976 by Easton and Sherman documented the effects of propranolol as a treatment for somatic symptoms of anxiety.  Authors mentioned that individuals with acute “anxiety attacks” are often evaluated extensively for various medical conditions, yet no diseases are found.  In most cases, these patients are dealing with somatic anxiety, or physical symptoms or sensations of stress.

The patients often ruminate upon these physical sensations, leading them to believe that they have a serious medical condition.  They then seek out medical care from a professional and are reassured that nothing is wrong.  Researchers speculate that beta-adrenergic hyperfunction may be a direct contributing cause of somatic anxiety.

In this publication, researchers describe 6 patients that they believed were suffering from somatic anxiety as a result of beta-adrenergic hyperactivity.  To stimulate beta-adrenergic hyperactivity and bolster somatic anxiety, researchers administered an infusion of isoproterenol hydrochloride to the 6 patients.  Thereafter, they administered propranolol and determined that it provided sustainable, long-term symptomatic relief.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/973806

1974: Response to propranolol and diazepam in somatic and psychic anxiety.

An early study published in 1974 by Tyrer and Lader compared responses to propranolol and Valium (diazepam) among individuals with somatic (physical) and psychological anxiety.  For the study, researchers recruited a total of 12 individuals that had been psychiatrically evaluated and diagnosed with chronic anxiety.  The 12 individuals were then administered: Inderal (propranolol), Valium (diazepam), or a placebo.

A balanced cross-over design was implemented and every patient received all three treatments separately, each on separate weeks.  In other words, Inderal was taken for one week, Valium for another week, and a placebo for the remaining week.  Anxiety levels were evaluated by a psychiatrist and participants after each aforestated treatment.

Results indicated that Valium (diazepam) was significantly more effective than propranolol and the placebo for alleviating anxiety.  However, propranolol was more effective than the placebo among individuals with somatic anxiety.  This suggests that propranolol is an effective intervention for individuals with somatic (physical) symptoms of anxiety, but unlikely helpful for those with chronic, psychological anxiety disorders.

• Source: http://www.ncbi.nlm.nih.gov/pubmed/4595181

Limitations associated with research of propranolol for anxiety

Although there’s a significant amount of research examining the anxiolytic efficacy of propranolol, many studies are of suboptimal quality.  Most studies have limited numbers of participants, lack robust designs (placebo-controlled, randomized, double-blind), implement outdated measures, and/or are conducted over an extremely short-term.  When contemplating the efficacy of propranolol as an anxiolytic, it is necessary to consider such research limitations.

• Adjunct: Most studies analyzed the efficacy of propranolol as a standalone intervention for anxiety. However, it may be helpful to evaluate its safety and anxiolytic potency when administered as an adjunct to another psychiatric medication.  For example, individuals with chronic anxiety that derive some benefit, albeit insufficient, from another intervention – may benefit from regular administration of propranolol.
• Anxiety subtypes: There are many subtypes of anxiety, each of which has a unique set of symptoms and neurophysiologic footprint. Many studies simply grouped all individuals with chronic anxiety disorders together and evaluated responses to propranolol, failing to consider that responses may vary based on the specific subtype of chronic anxiety.  Although some studies distinguished the effects of propranolol in “psychic” (psychological) and somatic (physical) anxiety, most didn’t.  Further research should attempt to elucidate the specific anxiety subtypes (e.g. generalized anxiety, social anxiety, hypochondriasis, PTSD, etc.) for which propranolol provides therapeutic benefit.  Types of anxiety most responsive to propranolol should then be distinguished from subtypes in which propranolol is ineffective.
• Conflicting results: While most studies suggest anxiolytic efficacy of propranolol for the management of somatic symptoms of anxiety, not all studies are in agreement upon whether propranolol treats psychological (psychic) symptoms of anxiety. Some research suggests that propranolol is ineffective for psychic anxiety, while other publications note its efficacy.  Further research may be warranted to elucidate propranolol’s efficacy in treating psychological anxiety and/or chronic anxiety disorders.
• Designs: In many studies, designs weren’t randomized, placebo-controlled, and double-blinded. To really understand whether propranolol is an effective anxiolytic, researchers will need to conduct larger-scale studies (with more participants) that have implemented robust designs.  Since some trials are not placebo-controlled, randomized, and/or double-blinded – conclusions deduced from the research could be considered of questionable accuracy.
• Lack of incentive: If propranolol were a new drug being pushed for the treatment of anxiety, large-scale clinical trials would be conducted to evaluate its efficacy. These trials would incorporate a significant number of participants and would implement a design that’s placebo-controlled, double-blinded, and randomized.  However, there’s no financial interest in evaluating propranolol as an anxiolytic – it is widely available as a generic and pharmaceuticals have no profit motive.  Therefore, new studies evaluating its efficacy are unlikely to be conducted and/or published.
• Measures: Some may consider the measures used to determine anxiety to be outdated and/or poor choices. Propranolol research conducted in the 1970s and 1980s may have utilized outdated anxiety measures that may be considered inadequate for a present-day study.  Additionally, some studies measured anxiety with self-reports and/or psychiatric evaluation.  It is therefore necessary to consider that results may be subject to slight inaccuracies.
• Questionable efficacy: Due to the small sample sizes and inadequate study designs, the efficacy of propranolol as an anxiolytic is under question. Although many studies have reported its efficacy as an anxiolytic intervention, results from these studies cannot be applied to clinical practices.  There are many already-effective anxiolytic drugs on the market that have been subject to rigorous scientific evaluation.  The quality of evidence from propranolol studies is lacking to recommend it as a first-line anxiolytic medication.
• Sample sizes: Without a large enough sample, it is difficult to gauge the accuracy of results from propranolol studies. The largest sample size in a propranolol study was 212 participants, but some of the participants were set to receive another drug or a placebo.  Participant numbers in most propranolol studies range from 6 to 60.  Small sample studies with poor designs can make it difficult to interpret results.
• Short-term studies: Most of the aforementioned studies of propranolol for anxiety were extremely short-term. Some reported that propranolol could be used over a long-term successfully, as evidenced by a patient taking propranolol with anxiolytic benefit for over 10 years, however, this was not part of an actual trial.  Many studies, such as those examining propranolol’s anxiolytic efficacy among patients undergoing medical surgery, tested the effects of propranolol over a single day.  There don’t appear to be many studies that have examined propranolol’s anxiolytic effects for longer than 1 month.
• Tolerance investigation: It is understood that propranolol users eventually become tolerant to its effects. Tolerance to propranolol will inevitably lead to an increase in dosage, and in time, the patient will likely become tolerant to their heightened dosage.  That said, it is unclear as to how long it takes (on average) for a patient to develop tolerance to propranolol’s effects.  It may be helpful to learn whether tolerance to propranolol can be avoided or delayed with strategic dosing protocols (e.g. taking it “as needed” or infrequently).

Verdict: Propranolol is an effective anxiolytic in certain cases

In nearly every aforementioned study, propranolol was considered an effective pharmacological treatment for anxiety.  However, due to limitations associated with the research, it is difficult to elucidate whether propranolol would be an effective first-line anxiolytic.  The most comprehensive review of evidence and meta-analysis was published in 2015 and noted that there is insufficient evidence to recommend propranolol as a treatment for anxiety.

Authors of the systematic review and meta-analysis didn’t undermine propranolol’s potential anxiolytic efficacy, they simply stated that there isn’t enough evidence to justify its usage as a treatment for anxiety.  That said, there are major limitations associated with this review of evidence, including that only a few studies met inclusion criteria.  This meant that there was an overwhelming lack of well-designed trials (placebo-controlled, double-blinded, randomized) examining propranolol as an anxiolytic.

Without considering the potentially myopic systematic review published in 2015, it appears as though propranolol is a viable treatment for anxiety, but not all types.  Research implies that propranolol is likely best suited to treat somatic anxiety, characterized by disconcerting physical sensations of anxiety, stress, and panic.  In addition, propranolol appears highly effective for the treatment of acute or transient anxiety associated with dentistry, surgery, and performance.

There is modest evidence to suggest its efficacy in attenuating psychological anxiety, school-refusal anxiety (among children), chronic anxiety disorders, and symptoms of PTSD.  Since propranolol likely addresses mostly physical symptoms, it should not be considered as a first-line intervention for debilitating, psychological anxiety.  However, it may be necessary to consider that among individuals exhibiting severe somatic and psychological anxiety, propranolol may serve as a practical adjunct treatment when prescribed with a first-line anxiolytic.

Upon comparison of propranolol to most other beta blockers (and even anxiolytics such as benzodiazepines), it appears to trigger fewer unwanted adverse reactions.  Compared to agents such as atenolol and Librium, propranolol is better tolerated and/or more efficacious.  In conclusion, propranolol may be an overlooked intervention for somatic anxiety, transient anxiety associated with medical procedures, and a subset of individuals with generalized anxiety disorders.

Benefits of Propranolol for Anxiety (Possibilities)

There are many potential benefits associated with using propranolol as a treatment for anxiety (compared to other interventions).  The most obvious benefit is that propranolol is highly effective as a treatment for somatic symptoms.  Additionally, propranolol can be taken over a long-term with sustained anxiolytic efficacy, and isn’t associated with significant unwanted side effects.

• Adjunct: Some individuals with anxiety derive significant benefit from the concomitant administration of an SSRI (or antidepressant) with propranolol as an adjunct. This pharmacological combination is capable of targeting both psychological symptoms of anxiety (via the SSRI) and somatic symptoms (via the propranolol).  Moreover, administration of propranolol as an adjunct doesn’t appear to attenuate the therapeutic efficacy of the SSRI.  Since there is minimal risk of interaction effects, and each substance addresses a unique aspect of anxiety, propranolol could be considered a feasible adjunct.
• “As needed”: Many propranolol users like the fact that it can be administered on an “as needed” basis. In other words, propranolol doesn’t need to be taken every single day like various antidepressants.  This allows individuals with anxiety to reserve propranolol usage for situations in which their anxiety is most severe.  If they would rather function without the influence of the drug, they can simply forgo propranolol usage without any consequences (e.g. withdrawal symptoms).
• Favorable over benzos: Benzodiazepines are highly effective for anxiety, but are clearly dangerous psychiatric drugs for numerous reasons. Benzodiazepines are associated with rapid tolerance onset, impairment of learning and/or memory, and coordination deficits.  Additionally, benzodiazepines have been linked to dementia, are addictive, and are controlled-substances – making it difficult for users to get prescription refills.  Propranolol may be favorable over benzodiazepines in that it isn’t considered addictive, has a slower onset of tolerance, and doesn’t impair cognitive processes (or coordination) to the same extent.
• Hypochondria: Individuals with hypochondria are often fixated on physical sensations that manifest as a result of anxiety. Since propranolol is highly effective for mitigating somatic anxiety, it should be thought to decrease severity of hypochondriasis.  If you are struggling with hypochondriasis and/or a nervous breakdown, and have failed to derive therapeutic benefit from traditional treatments, propranolol may be something to consider.
• Immediate relief: An advantage associated with using propranolol over other anxiolytics is that its therapeutic benefit is nearly instant. Users will derive significant anxiolytic benefit from propranolol within an hour or two of administration.  This means that you don’t need to wait 4 to 6 weeks for the drug to work as you would if taking an antidepressant.  Propranolol should alleviate anxiety on the very first day it is taken.
• Long-term: Propranolol is considered a fairly safe medication to use over the long-term. While no medication is devoid of long-term risk, there are some studies documenting cases of individuals that used propranolol for over 10 years for anxiety.  It is possible that propranolol, especially when used “as needed,” can provide therapeutic anxiolytic value over an extended (or prolonged) term.
• Performance anxiety: There’s some evidence to suggest that propranolol effectively attenuates symptoms of performance anxiety. One study conducted among ocular surgeons performing a microsurgery noted that the surgeons who took propranolol were more relaxed and exhibited fewer tremors than those who took a placebo.  Additionally, it is well-known that many high-profile musicians, stage-performers, and actors utilize propranolol for performance anxiety.
• Somatic anxiety: Individuals with somatic anxiety often report physical symptoms such as: butterflies in the stomach, sweating, muscular tension, heart palpitations, and headaches. Although somatic anxiety can be alleviated with traditional anxiolytic medications, traditional anxiolytics often address psychological anxiety and fail to address physical symptoms.  Propranolol is considered highly effective for the treatment of uncomfortable physical sensations associated with somatic anxiety.

Drawbacks of Propranolol for Anxiety (Possibilities)

Although there may be some advantages associated with using propranolol for anxiety, possible drawbacks should be discussed.  Some drawbacks encountered by individuals taking propranolol include: development of tolerance, failure to address cognitive/emotional symptoms, and experiencing unwanted side effects.  If you’ve contemplated using propranolol, you may want to review these drawbacks prior to treatment.

• Chronic anxiety disorders: Individuals with chronic anxiety disorders may not derive any benefit from propranolol. If you have a severe anxiety disorder, rather than transient anxiety, other options are thought to provide greater symptomatic relief (compared to propranolol).  Some research suggests that propranolol lacks efficacy among individuals with chronic, recurrent anxiety disorders.
• Cognitive deficits: It is necessary to consider that propranolol may affect cognitive function. Although it is not as cognitively-impairing as benzodiazepines, it can still cause brain fog and potentially compromise your executive function.  Some individuals like the anxiety relief they get from propranolol, but realize that their school and/or occupational performance suffers as a result of the drug.  You may not want to use propranolol if your livelihood depends on complex thinking, analysis, and problem solving.
• Ineffective: Due to major limitations associated with propranolol research, it is difficult to understand whether propranolol is actually an effective anxiolytic. It could be that propranolol is completely ineffective as an anxiolytic and unfit for clinical usage.  Though most research suggests it provides some benefit, whether the benefit is of therapeutic value isn’t known.
• Non-somatic symptoms: Individuals with cognitive and/or emotional anxiety may derive no benefit from propranolol. Propranolol and other beta blockers appear to be optimally suited for cases in which somatic anxiety is overwhelming.  Among users in which anxiety is rooted in cognitive and/or emotional processes, propranolol may be useless.  If you have anxiety, but no major physical symptoms, propranolol may be a suboptimal treatment.
• Side effects: There are many side effects that have been reported among propranolol users. Common propranolol side effects include: drowsiness, fatigue, insomnia, and weight gain. (Read more: “Propranolol & Weight Gain“).  It is also necessary to consider that propranolol may impair certain aspects of cognitive function and/or compromise one’s ability to operate heavy machinery.  Based on its side effect profile, some individuals may opt for a different anxiolytic treatment.
• Tolerance: As with any pharmaceutical treatment, taking propranolol for an extended duration is likely to result in tolerance. There are reports of individuals that build up neurophysiologic tolerance to the effects of propranolol and need to increase their dosage.  The more an individual increases his/her dosage, the greater the likelihood to experience unwanted side effects and/or adverse reactions.
• Withdrawal symptoms: Abrupt discontinuation of propranolol after ongoing, regular, long-term usage is likely to yield withdrawal symptoms. These symptoms may last weeks after the discontinuation date and manifest as: increased plasma catecholamines, elevated blood pressure, heart rate increases, and palpitations.  It is important to note that somatic anxiety may worsen during the withdrawal process.

Have you used Propranolol for anxiety?

If you’ve used propranolol for the treatment of anxiety, share your experience in the comments section below.  Mention the specific type of anxiety you were treating (e.g. performance, social, generalized, etc.) and the subjective efficacy of propranolol as an intervention.  Do you believe that propranolol is a superior intervention to other beta blockers commonly administered for anxiety?

Or have you found a beta blocker that works better than propranolol with fewer side effects?  To help others get a better understanding of your experience with propranolol, discuss your average dosage, frequency of usage, and the total duration over which you’ve used it.  Note whether you use propranolol as a standalone intervention or as part of a pharmaceutical cocktail or along with other dietary supplements.

When considering propranolol, an antihypertensive agent as a treatment for anxiety, it is necessary to note that other antihypertensives may be superior anxiolytic options (e.g. clonidine for anxiety).  That said, even without considering other options, there’s ample evidence to suggest efficacy of propranolol as a treatment for somatic anxiety.  Those with severe cases of somatic anxiety that respond poorly to other options may benefit from propranolol.

Related Posts:

• CBD Oil For Anxiety: Is Cannabidiol An Effective Treatment?
• Inositol For Anxiety Disorders: An Effective Treatment?
• Neurofeedback For Anxiety Disorders: An Effective Treatment?
• Beta Blockers For Anxiety Disorders
• Physical Symptoms Of Anxiety And Stress