Benzodiazepines and anxiety disorders: a risky bet

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), anxiety disorders are a group of mental disorders characterised by significant and ongoing feelings of worry and fear. They include agoraphobia, panic disorder, social phobia, and generalised anxiety disorder (American Psychiatric Association, 2013). They constitute the most prevalent subgroup of mental disorders, with up to 33.7% of the population affected during their lifetime (Bandelow & Michaelis, 2015).

Symptoms can be psychological, such as nervousness, or physical, involving the respiratory or gastrointestinal systems (Rakel, 1981). Because of the high variability in terms of triggers, symptom profiles, fears, and patient behaviours, many different psychological and pharmacological interventions are used in the treatment of anxiety, including but not limited to cognitive behavioural therapy, but also anxiolytics, antidepressants, antihistamines and antipsychotics (Bandelow et al., 2017).

In particular, benzodiazepines – a class of anxiolytics – have been commonly used for their fast-acting properties, with the anxiolytic effects beginning soon after administration (Stahl, 2002). This is especially useful in the case of acute panic attacks (Susman & Klee, 2005), allowing clinicians to calmly communicate with the patient (Bandelow et al., 2017). Benzodiazepines include drugs such as alprazolam, diazepam, lorazepam, with different absorption rates and half-lifes; for example, diazepam is rapidly absorbed and long lasting, while lorazepam has a slower and not as long-lasting effect (Anderson & McAllister-Williams, 2015).

GABA is a neurotransmitter that produces a calming effect on the brain (Fox et al., 2011). All benzodiazepines act on GABA receptors by binding to the GABAA receptor complex to lower the quantity of GABA needed to open the channel; this increase in efficiency produces similar anxiolytic effects to barbiturates and ethanol but with a much lower overdose risk profile (Nutt & Malizia, 2001). Thus, they have historically been one of the most frequently prescribed drug in the treatment of anxiety disorders, with high rates of long-term use of benzodiazepine (Stahl, 2002; Starcevic, 2014).

However, benzodiazepines are associated with problematic side effects when used over the long term, including development of physiological and psychological dependence, impaired cognition and coordination, and withdrawal syndromes (Chouinard, 2004; Nelson & Chouinard, 1999). Dependency may occur in patients after four to eight months of continued usage (Livingston, 1994; Shader & Greenblatt, 1993; Schweizer et al., 1990), and is more common in patients predisposed for substance abuse (Nelson & Chouinard, 1999; Schweizer et al., 1998).

In fact, benzodiazepines are characterised by a high abuse (or misuse) liability, meaning a high number of properties that facilitate people misusing it or becoming addicted to it (Ait-Daoud et al., 2018; Schatzberg, A. & DeBattista, 2015). As a result, between 58% and 100% of patients prescribed therapeutic doses of benzodiazepines long-term inadvertently become physically dependent (Ashton, 2005).

Furthermore, benzodiazepines can cause several cognitive, behavioural, emotional, and physical adverse effects. Common complaints include sleep deprivation, poor concentration, irritability, aggression, violence, self-destructive behaviour, and suicidality; many patients with mental health problems struggle with these symptoms already, which makes their presence on the list of potential side effects of benzodiazepines problematic (Guina & Merrill, 2018). Physical adverse effects include sedation, unsteadiness, and slurred speech (Pary & Lewis, 2008). Use of benzodiazepines can even be fatal to the patient, whether directly by overdose or indirectly by injury (Guina & Merrill, 2018).

Due to these adverse effects, benzodiazepines are no longer considered the primary therapy for anxiety disorders. Instead, selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are recommended as the first-line pharmacological treatments of choice (Bandelow et al., 2014; Locke et al., 2015). Why then, despite their high risk of misuse and physical dependence, are benzodiazepines still some of the most commonly prescribed drugs for anxiety disorders (Ashton, 2005; Bushnell, et al., 2017)?

Serotonergic agents – typically used in depression – take between four to six weeks to exert clinical effect (Fava et al., 2008). When these treatments are started, it is not uncommon for clinicians to co-prescribe benzodiazepines as adjuncts in the first few weeks before a therapeutic dose is achieved, despite the lack of evidence supporting this practice (Bushnell, et al., 2017; Dunlop & Davis, 2008). Worst, many patients receive benzodiazepines for long-term treatment without ever being prescribed any of the recommended first-line treatments (Guina & Merrill, 2018).

While benzodiazepines can be useful in very specific cases, it appears that more education is needed to ensure that the right treatment is prescribed to the right patients, and for the appropriate duration.


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