Benzodiazepine long-term treatment

Benzodiazepines are used commonly in SAD however, there are limited data supporting their use. Clonazepam has been effective for social anxiety, fear, and phobic avoidance, and it reduced social and work disability during acute treatment.58 Long-term treatment is not desirable for many SAD patients owing to the risk of withdrawal and difficulty with discontinuation, cognitive side effects, and lack of effect on depressive symptoms. Benzodiazepines may be useful for acute relief of physiologic symptoms of anxiety when used concomitantly with antidepressants or psychotherapy. Benzodiazepines are contraindicated in SAD patients with alcohol or substance abuse or history of such. 

The development of tolerance is a major drawback to the use of benzodiazepines in the long-term treatment of insomnia. Whereas tolerance to the hypnotic effects of benzodiazepines permits them to be used without excessive sedation when treating anxiety disorders, this is counterproductive when attempting to treat insomnia. Patients often find themselves requiring higher doses to obtain the same sedative-hypnotic effect initially accomplished by lower doses. For this reason, careful consideration must be given before benzodiazepines are used to treat chronic insomnia. 

Benzodiazepines. Longer-acting clonazepam and shorter-acting alprazolam have also been used in the treatment of social anxiety disorder, and controlled trials have shown them to be quite effective. In our experience, alprazolam is best suited for discrete periods of intermittent anxiety, though both clonazepam and the new long-acting alprazolam (Xanax XR) are likely effective for long-term treatment. 

Several preliminary lines of research have started to suggest that antidepressants, once considered ineffective in generalized anxiety disorder, may be very efficacious [Gorman and Kent 1999]. In particular, venlafaxine has been effective in treating generalized anxiety disorder in both open-label and double-blind trials, and imipramine and paroxetine were as effective as a benzodiazepine in the long-term treatment of generalized anxiety disorder. 

Another alternative is buspirone, a non-benzodiazepine anxiolytic that seems to be free of untoward effects on cognitive performance (Ninan et ul., 1998). As indicated in Chapter 1, the anxiolytic effect of this compound ma take a few weeks to occur (and is often rather weak), meaning that buspirone is better suited for long-term treatment of anxiety syndromes than for immediate anxiolvsis. 

Uhlenhuth EH, Balter MB, Ban TA, et al. International study of expert judgment on therapeutic use of benzodiazepines and other psychotherapeutic medications IV. Therapeutic dose dependence and abuse liability of benzodiazepines in the long-term treatment of anxiety disorders. J Clin Psychopharmacol 1999 19(suppl 2) 23S-29S. 

The benzodiazepines (see Chapter 22) provide much more rapid relief of both generalized anxiety and panic than do any of the antidepressants. However, the antidepressants appear to be at least as effective and perhaps more effective than benzodiazepines in the long-term treatment of these anxiety disorders. Furthermore, antidepressants do not carry the risks of dependence and tolerance that may occur with the benzodiazepines. 

Currently, many physicians adopt a benzodiazepine-sparing strategy by using benzodiazepines when necessary but conservatively. That is, benzodiazepines can often be helpful when treatment is initiated or when a rapid-onset therapeutic effect is desired. They can also help improve the short-term tolerability of SSRIs by blocking the jitteriness and exacerbation of panic sometimes observed when initiating treatment with an SSRI or other antidepressant. Benzodiazepines can also be useful to top up the patient s treatment on an as-needed basis for sudden and unexpected decompensation or short-term psychosocial stressors. Finally, if a patient is not fully responsive to an antidepressant or combinations of antidepressants, long-term treatment with concomitant benzodiazepines and antidepressants may become necessary to effect full or adequate control of symptoms. Sometimes, once symptoms are suppressed for several months to a year, the benzodiazepine can be slowly discontinued and the patient maintained long-term on the antidepressant alone. The consequences of inadequate treatment of panic disorder can be very severe loss of social and oc-... 

Several members of the benzodiazepine group are effective in treating epilepsy, but most are limited because of problems with sedation and tolerance. Some agents such as diazepam (Valium) and lorazepam (Ativan) are used in the acute treatment of status epilepti-cus (see Treatment of Status Epilepticus ), but only a few are used in the long-term treatment of epilepsy. Clonazepam (Klonopin) is recommended in specific forms of absence seizures (e.g., the Lennox-Gastaut variant) and may also be useful in minor generalized seizures such as akinetic spells and myoclonic jerks. Clorazepate (Tranxene) is another benzodiazepine that is occasionally used as an adjunct in certain partial seizures. 

In general, the better safety profile of the newer generation nonbenzodiazepines, for example, zaleplon compared to benzodiazepines, makes them better first-line choices for long-term treatment of chronic insomnia [39]. 

The anesthetic effect of (+)-etomidate subsides within a few minutes owing to redistribution of the drug. Etomidate can provoke myoclonic movements that can be prevented by premedication with a benzodiazepine or an opioid. Because it has little effect on the autonomic nervous system, it is suitable for induction in combination anesthesia. Etomidate inhibits cortisol synthesis in subanesthetic doses and can therefore be used in the long-term treatment of adrenocortical overactivity (Cushing disease). 

Ferenci P, Grimm G, Meryn S, Gangl A. Successful long-term treatment of portal-systemic encephalopathy by the benzodiazepine antagonist flumazenil. Gastroenterology 1989 96 240-3. 

Madder SA, Schweizer E. Benzodiazepines as anxiolytic agents the risks of long-term treatment. Hospital Practice 1992 September 30, 109-16. 

A large number of benzodiazepines have broad antiseizure properties, but only clonazepam (Klonopin) and clorazepate (Tranxene-SD, others) have been approved in the United States for the long-term treatment of certain types of seizures. Diazepam (Valium, Diastat, others) and lorazepam (Ativan) have well-defined roles in the management of status epilepticus. 

MANAGEMENT OE PATIENTS AETER LONG-TERM TREATMENT WITH HYPNOTIC AGENTS If a benzodiazepine has been used regularly for more than 2 weeks, it should be tapered rather than discontinued abruptly. In some patients on hypnotics with a short tj it i easier to switch first to a hypnotic with a long t and then to taper. 

A 52-year-old woman on long-term treatment with benzodiazepines experienced confusion and auditory and visual hallucinations within 2 days of starting to take kava (Cartledge and Rutherford 2001). Several case reports of possible dopamine antagonism suggest that kava may interact with central dopamine agonists or antagonists (Mills and Bone 2005 Schelosky et al. 1995). 

Petursson H, Lader MH Benzodiazepine dependence. BrJ Addict 76 133—143,1981a Petursson H, Lader MH Withdrawal from long-term benzodiazepine treatment. Br Med J (Clin Res Ed) 283 643—643, 1981b Pichard L, Gillet G, Bonfils C, et al Oxidative metabolism of zolpidem by human liver... 

Vorma H, Naukkarinen H, Sarna S, et al Long-term outcome after benzodiazepine withdrawal treatment in subjects with complicated dependence. Drug Alcohol Depend 70 309-314, 2003... 

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