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Current P SYCHIATRY Current p SYCHIATRY Benzodiazepines for substance abusers Yes? No? Do addiction worries outweigh the need for effective anxiety treatment? A sobriety-based algorithm addresses both concerns. S. Pirzada Sattar, MD ow should you treat anxiety in substance- Assistant professor of psychiatry H abusing patients: deny them benzodi- Associate director of residency training azepines and risk under-treatment, or Creighton/University of Nebraska psychiatry prescribe benzodiazepines for the anxiolytic residency program effect and risk contributing to addiction? Staff psychiatrist, Substance Abuse Treatment Center VA Medical Center, Omaha, NE There is no definitive answer, but one thing is clear: Among psychiatric patients, substance Subhash Bhatia, MD abusers are most likely to abuse benzodiazepines and become addicted to them. Professor of psychiatry Creighton University School of Medicine Some argue that the abuse potential is over- Chief of Mental Health and Behavioral Science stated, but only limited data suggest that benzo- VA Medical Center, Omaha, NE diazepines can be safely prescribed to patients who are abusing alcohol or drugs. In this article, we discuss benzodiazepine use in these patients and offer a sobriety-based treatment approach. continued VOL. 2, NO. 5 / MAY 2003 25 Benzodiazepines Table 1 benzodiazepine and cloza- Benzodiazepines’ potency and half-lives, pine.1 including half-lives of active metabolites Overdose and withdrawal symptoms. Benzodiazepine Potency Shorter half-life (hr) Longer half-life (hr) overdose is characterized by slurred speech, seda- High Alprazolam (6 to 12) Clonazepam (18 to 50) tion, memory impairment, Lorazepam (10 to 20) incoordination, respirato- Triazolam (2) ry depression, hypoten- Low Oxazepam (4 to 15) Chlordiazepoxide (5 to 30) [36 to 200]* sion, stupor, and coma. Temazepam (8 to 22) Clorazepate [36 to 200]* Abrupt withdrawal may produce life-threatening Diazepam (20 to 100) [36 to 200]* delirium, hallucinations, Flurazepam [40 to 250]* grand mal seizures, and * [active metabolite] symptoms similar to those Source: Ashton CH. Benzodiazepine equivalence table. Available at www.benzo.org.uk of alcohol withdrawal (insomnia, anxiety, tremor, hyperactivity, nausea, BENEFITS AND RISKS vomiting, and psychomotor agitation).1 Considered a safe substitute for barbiturates, ben- zodiazepines were heralded as wonder drugs ABUSE PATTERNS when they were introduced in the 1950s. Reports The few empiric studies examining benzodi- of their addictive potential surfaced in the 1970s, azepines’ abuse potential in substance abusers and since then researchers have disagreed on have shown inconsistent results. However, it is whether benzodiazepines should be prescribed to generally accepted that: substance-abusing or -dependent patients. • long-term benzodiazepine use may lead Clinical utility. Benzodiazepines are used in many to tolerance and physiologic dependence clinical situations because of their: • withdrawal symptoms can occur if benzo- • anxiolytic, hypnotic, anticonvulsant, diazepines are stopped suddenly, especially antipanic, antidepressant, amnestic, anes- after long-term (months to years) use. thetic, and antispastic effects Even though most benzodiazepine prescrip- • relatively mild side effects, when com- tions are not abused,2 a history of alcohol and pared with alternatives such as barbiturates. drug abuse suggests high potential for benzodi- In psychiatry, benzodiazepines are used to azepine abuse. Also, long-term users of pre- treat anxiety disorders, agitation, and insomnia. scribed benzodiazepines often develop tolerance Because of cross-tolerance with alcohol and bar- and may escalate their doses to get the same biturates, benzodiazepines also are used to man- desired effects. If their supply is threatened, these age alcohol or barbiturate withdrawal. patients may seek benzodiazepines illicitly. Interactions. Benzodiazepines can interact with Benzodiazepines may enhance or prolong other psychotropics, including lithium, antipsy- the elation (“high”) associated with other drugs chotics, and selective serotonin reuptake or mitigate the depression (“crash”) that follows a inhibitors (SSRIs). Respiratory arrest has been stimulant “high.” Sometimes benzodiazepines reported in patients taking both a high-potency are the drug of choice, as high doses of potent, continued on page 29 26 Current VOL. 2, NO. 5 / MAY 2003 p SYCHIATRY Current p SYCHIATRY continued from page 26 short-acting agents may provide a Table 2 stimulant “high.” Should benzodiazepines be prescribed to substance abusers? WHO ABUSES BENZODIAZEPINES? Alcohol and substance abusers tend YES: Arguments for to ingest benzodiazepines for recre- • Studies showing risks of benzodiazepine abuse ational purposes. Thirty to 50% of in substance users were based on faulty data alcoholics undergoing detoxification (Maletzky & Klotter).17 and 44% of IV drug abusers also • Long-term benzodiazepine treatment of anxiety— may be abusing benzodiazepines.3 even in substance abusers—is similar to treatment Benzodiazepines are cross-toler- of other chronic conditions (Lader).18 ant with alcohol, and alcoholics may • Studies suggesting that alcoholics and drug use them with alcohol or as a substi- abusers are at high risk of benzodiazepine abuse tute when alcohol is unavailable. are inconclusive (Ciraulo et al).19 They also may self-medicate with • Abuse potential is minimal, and undue restrictions benzodiazepines to ease alcohol’s cause patients to suffer needlessly (Berner).20 withdrawal symptoms. Opiate, am- • Prolonged benzodiazepine use decreases morbidity in phetamine, and cocaine abusers may chronic conditions (Schatzberg).21 use benzodiazepines with their drugs • Other treatments are often ineffective (Lader).22 of choice, as may younger abusers of NO: Arguments against MDMA (“Ecstasy”) and LSD. • Prescribing benzodiazepines promotes drug abuse Even patients who begin taking (Sellers et al).23 benzodiazepines for legitimate rea- • Physiologic tolerance and dependence occurs with sons may end up abusing them. In every long-term benzodiazepine use, and these risks 24 one study of 2,600 patients prescribed are compounded in substance abusers (Hamlin). diazepam, up to 60% had abused • Long-term benzodiazepine use may cause structural brain damage (Piesiur-Strehlow et al).25 and/or become dependent on it.4 Benzodiazepine abuse may start • Guilt and failure to spend enough time with patients with other sedative/hypnotic abuse are the main reasons physicians prescribe benzodi- 26 or as experimentation with drugs or azepines (Bendtsen et al). alcohol, typically around age 13 or • Benzodiazepines should be reserved for detoxification and withdrawal in individuals with 14.5 The average benzodiazepine type 2 alcoholism (Linnoila).27 abuser is age 19 to 31, and the male- to-female ratio is about 2:1.6 Multi-drug abuse. Benzodiazepines are usually not the preferred or sole previous week.8 Other studies suggest that up to drug of abuse. Roughly 80% of benzodiazepine 90% of methadone users regularly abuse benzodi- abuse may be a component of poly-drug abuse, azepines, often at high doses.9 most commonly with opioid addiction.7 A 2-year National Institute on Drug Abuse study of heroin ILLICIT USE POTENTIAL abusers suggested that 15% also abused benzodi- Prescriptions are the primary source of supply for azepines daily for more than 1 year, and 73% had benzodiazepine abusers. These patients are doc- abused benzodiazepines several times during the tor shoppers and often change pharmacies. They VOL. 2, NO. 5 / MAY 2003 29 Benzodiazepines visit emergency rooms frequently and may feign diazepoxide has been reported to produce a lower symptoms to obtain benzodiazepine prescrip- “high” than other benzodiazepines.14 Among the tions. They fill prescriptions for personal use or short half-life benzodiazepines, oxazepam may sell the drugs to illicit sources to support their have a relatively low abuse potential.14 Clon- addictions. azepam—a high-potency benzodiazepine with a long half-life—is gener- Without convincing data, psychiatrists must decide ally safe and may have a the merits of using benzodiazepines, usually case by case. lower abuse or addiction potential, although its abuse has been report- On the street, brand-name benzodiazepines ed.15 Similarly, oxazepam, clorazepate, and chlor- are worth much more than generics because they diazepoxide may be less reinforcing than other can be identified by photographs of brand-name benzodiazepines, although reports have linked benzodiazepines on the Internet or in reference these agents to abuse as well.16 books. In many cities, the street value of the Xanax or Klonopin brands may be $5 to $10 per pill. A 5- TO PRESCRIBE OR NOT TO PRESCRIBE mg tablet of Valium-brand diazepam may sell for Opponents blame benzodiazepines for promot- $5, and 10-mg tablets are worth up to $10. ing the drug culture and argue that prescribing Higher abuse potential. All benzodiazepines have benzodiazepines promotes drug abuse. Advocates abuse potential, and most have been reported in of benzodiazepine therapy contend that restrict- the literature as being abused. Those most likely ing an effective and safe medication is unethical, to be abused have a short half-life10 (Table 1) or even in substance abusers. Arguments from each rapidly cross the blood brain barrier, such as perspective are summarized in Table 2.17-27 alprazolam.11 In 1990, an American Psychiatric Association Alprazolam and lorazepam are popular task force concluded that
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