Cons. Although widely prescribed—and despite their efficacy in numerous conditions— both acute or long-term benzodiazepine use frequently causes adverse effects.4 Patients may develop tolerance, which can lead to escalating dosages and/or to withdrawal symptoms when patients attempt to cut back. Benzodiazepines eventually become ineffective for sleep, and continued use can cause rebound insomnia. Also, with many patients taking benzodiazepines long-term, clinicians struggle to differentiate between “real” anxiety symptoms and subtle states of withdrawal from fluctuating benzodiazepine blood levels.5
Geriatric patients who take benzodiazepines are at risk for falls and hip fractures.4 Although older dementia patients are at particular risk for cognitive problems— including frank delirium—secondary to benzodiazepine use, patients of all ages are susceptible to these medications’ deleterious neurocognitive effects.
Benzodiazepines can lead to excessive sedation, thereby impairing performance at work or school, and have been implicated as a cause of motor vehicle accidents.6 Finally, a serious drawback to benzodiazepine use is possible lethality in overdose, especially when combined with alcohol.
Benzodiazepine prescribing should not be taken lightly. Always analyze the difference between benzodiazepines’ well-documented efficacy and their adverse effect profile. This risk-benefit analysis becomes much more complex for patients with SUDs.
Special considerations. Patients at higher risk for benzodiazepine abuse include those with:
- severe alcohol dependence (ie, long-term use, drinking since a young age [“Type II”])
- intravenous drug use
- comorbid alcoholism and antisocial personality disorder.7,8
Exercise special caution when considering benzodiazepines for patients with severe psychiatric illness such as schizophrenia-spectrum disorders, bipolar disorder, or severe depression. Patients with schizophrenia have high rates of alcohol, cocaine, cannabis, and benzodiazepine abuse.9,10 Bipolar disorder patients show similar vulnerability—up to 56% of patients screen positive for substance abuse or dependence.11 Vulnerability to addiction in severely ill psychiatric patients is thought to be related to several factors, including:
- use of drugs as self-medication
- genetic predisposition
- environment/lifestyle that supports substance abuse
- neurobiologic deficits that lead to lack of inhibition of reward-seeking behaviors.11
Bipolar disorder patients in particular score high on measures of sensation seeking, which leaves them vulnerable to abusing all classes of substances.12
In a 6-year study of 203 patients with severe psychiatric illnesses and SUDs, Brunette et al13 found that these patients were 2.5 times more likely than patients with severe psychiatric illness alone to abuse prescribed benzodiazepines. In an analysis of Medicaid records, Clark et al14 found similar vulnerability in patients with major depressive disorder (MDD) and SUD. Not only did these patients show a higher rate of benzodiazepine use than patients with MDD without SUD, but the dual-diagnosis group also gravitated toward more addictive high-potency/fast-acting benzodiazepines, such as alprazolam, estazolam, or triazolam.
Case discussion/suggestions. Initially, Mr. A may seem to be an appropriate candidate for closely monitored benzodiazepine use. However, he shows a pattern of misuse, likely related to his history of severe alcohol dependence and alprazolam use. This benzodiazepine is fast-acting and has a short half-life, and thus is highly reinforcing.
Similarly, Ms. B might benefit from benzodiazepine treatment. However, her history of schizophrenia and alcohol abuse makes her a risky candidate, and alternative treatments for anxiety symptoms should be considered. If prescribed at all, a benzodiazepine should be used only short-term (eg, 1 to 2 weeks).
In general, avoid prescribing benzodiazepines to most patients who have an ongoing or past SUD.15 Consider making an exception for SUD patients with comorbid anxiety disorders, with close monitoring of their benzodiazepine use. Clonazepam, chlordiazepoxide, clorazepate, and oxazepam may be less reinforcing for SUD patients than diazepam, lorazepam, alprazolam, estazolam, or triazolam.7,16 The drawbacks of benzodiazepines, especially in the situations described above, point to the need to find alternative treatments (Table 2).17 Keep in mind nonpharmacologic options, which completely avoid the risks of medication misuse and diversion. Cognitive-behavioral therapy (CBT), for instance, has well-documented efficacy in treating insomnia and anxiety disorders.18,19
Table 2
Alternatives to benzodiazepines for anxiety and/or insomnia
| Treatment option | Comments |
|---|---|
| CBT, relaxation techniques, sleep hygiene counseling | Many advantages to nonpharmacologic interventions (eg, fewer side effects, no risk of substance dependence) |
| Antihistamines (eg, diphenhydramine, 25 to 50 mg at bedtime* for sleep, or 2 to 3 times a day for anxiety) | Can be used for anxiety or insomnia; can cause confusion in older patients |
| Atypical antipsychotics | Off-label use; many agents in this class have metabolic side effects |
| SSRIs/SNRIs | First-line for many anxiety disorders, including panic disorder, GAD; possible weight gain and sexual side effects |
| Mirtazapine (7.5 to 30 mg at bedtime*) | Sedation side effect helps with sleep; weight gain and oversedation limit use |
| Trazodone (25 to 100 mg at bedtime*) | Commonly used off-label as a sleep aid |
| Monoamine oxidase inhibitors | May be useful for social phobia; dietary restrictions and side effects limit use |
| Doxepin (3 to 6 mg at bedtime) | Minimal anticholinergic and alpha-blockade side effects at this dose; FDA-approved for insomnia |
| Gabapentin (300 to 2,000 mg/d* in divided doses) | Off-label use, mild anxiolytic and sedative properties, relatively weight neutral |
| Beta blockers (eg, propranolol, 20 to 80 mg twice a day*) | Useful for peripheral manifestations of anxiety; may be effective for social phobias |
| Pregabalin (50 to 200 mg 3 times a day*) | Off-label use; industry-sponsored studies show comparable to SNRIs for anxiety |
| Non-benzodiazepine GABAA receptor modulators | Short-term option for primary insomnia, some abuse potential |
| Melatonin (1 to 3 mg at bedtime*) | Mild and ‘natural’ but not always an effective sleep aid |
| *Off-label approximate doses based on the authors’ clinical experience and consensus of the literature; agents listed may require slow titration and close monitoring for adverse effects CBT: cognitive-behavioral therapy; GABA: gamma-aminobutyric acid; GAD: generalized anxiety disorder; SNRI: serotoninnorepinephrine reuptake inhibitor; SSRI: selective serotonin reuptake inhibitor Source: Reference 17 | |