Jeannette Y. Wick, R.Ph., MBA, FASCP
One in 4 adults will suffer from a diagnosable anxiety disorder at some point in life.2,3 Anxiety can create substantial emotional and physical discomfort, and epidemiological studies indicate that anxiety is often linked to a higher likelihood of mental illnesses and substance abuse. When anxiety is comorbid with psychiatric disorders, patients tend to have an elevated suicide risk and more resistant disease.2,3
Anxiety’s core features are excessive fear and worry.4 The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) indicates that anxiety takes many forms (see TABLE 14).4
Traditionally, benzodiazepines have been effective for anxiety and widely used. Increasingly, guidelines recommend avoiding this class because of its addiction potential. Benzodiazepine prescribing rates correlate significantly with benzodiazepine coinvolvement in overdose deaths from opioids.5
Multiple randomized controlled trials have shown that serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors can ameliorate generalized anxiety disorder (GAD), panic disorder (PD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD),6-9 with response rates in GAD generally better than in other anxieties.7,9,10 However, response rates are variable and anxiety is a diagnosis for which new treatments are sorely needed.
Some older drugs are used. Buspirone is FDA approved as monotherapy for anxiety but is usually used to augment other drugs. Studies that enrolled patients with GAD have found it as effective as diazepam and sertraline but less effective than venlafaxine.11-13 Hydroxyzine is used for short-term treatment of anxiety. Its efficacy is often mitigated by its propensity to cause sedation.14 TABLE 215 summarizes frequently used medications.
The European Medicines Agency has approved pregabalin for anxiety and European prescribers use it often. The FDA has not approved pregabalin, which is schedule V in the United States, for anxiety, but some prescribers may use it off-label.16,17 Similarly, prescribers sometimes use gabapentin for anxiety. Pharmacists should note that widespread abuse of gabapentin for its euphoric effects at high doses has forced some states to move it to controlled drug status.18
If preferred treatments are ineffective alone or in combination, some prescribers will use second-generation antipsychotics, especially quetiapine. Their adverse effects— such as akathisia, metabolic aberrations, sedation, weight gain, and, rarely, tardive dyskinesia—limit their utility.19,20
Individuals who do not seek treatment for anxiety and even some who do often abuse or use alcohol to self-medicate.21 In addition to being potentially addictive, alcohol can damage the liver and may predispose individuals to arrhythmias. It is also disinhibiting, especially troublesome combined with benzodiazepines and opioids lethal in overdosage, and sedating.21
Manufacturers that market cannabidiol (CBD) products without FDA approval have promoted these products for anxiety.22 Studies have not evaluated CBD in PD, separation, or specific phobias, and in studies of the anxiety response of healthy volunteers, as well as those with GAD, PTSD, and SAD, doses have been widely divergent as have been administration routes. Pharmacists should remind patients that it is impossible to determine these products’ efficacy, potency, purity, and safety.22
Helping patients who have anxiety see that they should pursue treatment can be challenging, because they are often hesitant. One way to approach the topic is to point out that seeking help also helps those around them. Anxiety is contagious, in a sense. Individuals who are around others who are anxious often report feeling increasingly anxious.23 Much like explaining to people that being immunized or wearing a mask helps others, explaining this to people with anxiety can show them that treatment may improve their family and social dynamics. It is important to remind patients that in addition to medication adherence, engagement in pleasurable activities can reduce anxiety.
JEANNETTE Y. WICK, RPH, MBA, FASCP, is the assistant director of the Office of Pharmacy Professional Development at the University of Connecticut School of Pharmacy in Storrs.
- Kessler RC, Chiu WT, Demler O, Merikangas, KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry.2005;62(6):617-627. doi:10.1001/archpsyc.62.6.617
- Schaffer A, McIntosh D, Goldstein BI, et al. The CANMAT task force recommendations for the management of patients with mood disorders and comorbid anxiety disorders. Ann Clin Psychiatry. 2012 24(1):6-22.
- Nepon J, Belik SL, Bolton J, Sareen J. The relationship between anxiety disorders and suicide attempts: Findings from the national epidemiologicsurvey on alcohol and related conditions. Depress Anxiety. 2010;27(9):791-798. doi:10.1002/da.20674
- Diagnostic and statistical manual of mental disorders, 5th ed. American Psychiatric Association;2013.
- Tori ME, Larochelle MR, Naimi TS. Alcohol or benzodiazepine co-involvement with opioid overdose deaths in the United States, 1999-2017. JAMA Netw Open. 2020;3(4):e202361. doi:10.1001/jamanetworkopen.2020.2361
- Stein MB, Stein DJ. Social anxiety disorder. Lancet. 2008;371(9618):1115-1125.
- Baldwin DS, Waldman S, Allgulander C. Evidence-based pharmacological treatment of generalized anxiety disorder. Int J Neuropsychopharmacol. 2011;14(5):697-710.
- Cuijpers P, Sijbrandij M, Koole SL, Andersson G, Beekman AT, Reynolds CF III. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: A meta-analysis of direct comparisons. World Psychiatry. 2013;12(2):137-148
- Stein DJ, Ipser JC, Seedat S, Sager C, Amos T, Cochrane Common Mental Disorders Group Pharmacotherapy for post traumatic stress disorder (PTSD). Cochrane Database Syst Rev.2006(1):CD002795. doi:10.1002/14651858.CD002795.pub2
- Otto MW, Tuby KS, Gould RA, McLean RY, Pollack MH. An effect-size analysis of the relative efficacy and tolerability of serotonin selective reuptake inhibitors for panic disorder. Am J Psychiatry.2001;158(12):1989-1992.
- Feighner JP, Merideth CH, Hendrickson GA. A double-blind comparison of buspirone and diazepam in outpatients with generalized anxiety disorder. J Clin Psychiatry. 1982;43(12 Pt 2):103-108.
- Cohn JB, Rickels K. A pooled, double-blind comparison of the effects of buspirone, diazepam and placebo in women with chronic anxiety. Curr Med Res Opin. 1989;11(5):304-320. doi:10.1185/03007998909115213
- Mokhber N, Azarpazhooh MR, Khajehdaluee M, Velayati A, Hopwood M. Randomized, single-blind, trial of sertraline and buspirone for treatment of elderly patients with generalized anxiety disorder. Psychiatry Clin Neurosci. 2010;64(2):128-133. doi:10.1111/j.1440-1819.2009.02055.x
- Guaiana G, Barbui C, Cipriani A. Hydroxyzine for generalised anxiety disorder. Cochrane Database Syst Rev. 2010;(12):CD006815. doi:10.1002/14651858.CD006815.pub2
- Murrough JW, Yaqubi S, Sayed S, Charney DS. Emerging drugs for the treatment of anxiety. Expert Opin Emerg Drugs. 2015;20(3):393-406. doi:10.1517/14728214.2015.1049996
- Baldwin DS, Ajel K, Masdrakis VG, Nowak M, Rafiq R. Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatr Dis Treat. 2013;9:883-892. doi:10.2147/NDT.S36453
- Greenblatt HK, Greenblatt DJ. Gabapentin and pregabalin for the treatment of anxiety disorders. Clin Pharmacol Drug Dev. 2018;7(3):228-232. doi:10.1002/cpdd.446. PMID: 29579375
- McPherson D, Wick JY. Gabapentin: change is in the wind. Sr Care Pharm. 2019;34(8):490-498
- Maneeton N, Maneeton B, Woottiluk P, et al. Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials. Drug Des Devel Ther. 2016;10:259-276. doi:10.2147/DDDT.S89485
- Kreys TM, Phan SV. A literature review of quetiapine for generalized anxiety disorder. Pharmacotherapy.2015;35(2):175-188. doi:10.1002/phar.1529
- Anker JJ, Kushner MG. Co-occurring alcohol use disorder and anxiety: bridging psychiatric, psychological, and neurobiological perspectives. Alcohol Res. 2019;40(1):arcr.v40.1.03. doi:10.35946/arcr.v40.1.03
- Skelley JW, Deas CM, Curren Z, Ennis J. Use of cannabidiol in anxiety and anxiety-related disorders. J Am Pharm Assoc (2003).2020;60(1):253-261. doi:10.1016/j.japh.2019.11.008
- Dimitroff SJ, Kardan O, Necka EA, Decety J, Berman MG, Norman GJ. Physiological dynamics of stress contagion. Sci Rep. 2017;7(1):6168. doi:10.1038/s41598-017-05811-1