Benzodiazepines alternatives

Barbiturate The family name for a group of drugs with anticonvulsant, anaesthetic and sedative-hypnotic properties. Examples include amylobarbitone and pheno-barbitone. The problem of dependence and the introduction of safer benzodiazepine alternatives has resulted in a marked reduction in their clinical use. 

Panic disorders are sudden attacks of severe anxiety accompanied or even dominated by physical symptoms such as heart palpitations, difficulty in breathing and a constrictive feeling in the chest, which can intensify the anxiety attack and put the subject m fear of his life. Panic attacks often arise spontaneously without detectable cause or are associated with particular situations such as being in a crowd, in a small, enclosed space or on an exposed street. Both syndromes can be treated successfully with benzodiazepines. Alternatives to tranquillizers include certain antidepressants, e.g. SSRIs, and non-drug therapeutic procedures (see below). 

Wagner J, Wagner ML, Hening WA. Beyond benzodiazepines alternative pharmacologic agents for the treatment of insomnia. Ann Pharmacother 1998 32 680-691. 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

Disulfiram inhibits CYP enzymes 1A2, 2C9, and 3A4 many benzodiazepines are metabolized via these pathways lorazepam, temazepam, and oxazepam are NOT metabolized via the CYP4S0 system and are reasonable alternatives. 

Benzodiazepines are the evidence-based treatment of choice for uncomplicated alcohol withdrawal.17 Barbiturates are not recommended because of their low therapeutic index due to respiratory depression. Some of the anticonvulsants have also been used to treat uncomplicated withdrawal (particularly car-bamazepine and sodium valproate). Although anticonvulsants provide an alternative to benzodiazepines, they are not as well studied and are less commonly used. The most commonly employed benzodiazepines are chlordiazepoxide, diazepam, lorazepam, and oxazepam. They differ in three major ways (1) their pharmacokinetic properties, (2) the available routes for their administration, and (3) the rapidity of their onset of action due to the rate of gastrointestinal absorption and rate of crossing the blood-brain barrier. 

For cyanide and cyanogen, antidote should be administered as soon as possible. The Lilly Cyanide Antidote Kit contains amyl nitrite, sodium nitrite, and sodium thiosulfate. Cobalt edentate or 4-dimethylaminophenol are alternative antidotes for cyanide poisoning. Benzodiazepines or barbiturates may be required to control severe seizures. 

First, optimize current mood stabilizer or initiate mood-stabilizing medication lithium,0 valproate,0 or carba-mazepine0 Consider adding a benzodiazepine (lorazepam or clonazepam) for short-term adjunctive treatment of agitation or insomnia if needed Alternative medication treatment options carbam-azepine0 if patient does not respond or tolerate, consider atypical antipsychotic (e.g., olanzapine, quetiapine, risperidone) or oxcarbazepine. 

High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. 

The antidepressants are good alternatives for patients with poor sleep who should not receive benzodiazepines, especially those with depression or a... 

Before initiating any pharmacotherapy the patient should be asked about sleep-wake patterns, napping etc. Disturbed sleep is common among elderly (Vitiello 1997). In a study on persons 81 years or older, more than one third had problems with their sleep (Giron et al. 2002). There are better tolerated pharmacological alternatives than benzodiazepines (Hemmeter et al. 2000) and many times identifying problems that cause the sleep disturbance may solve the problem. 

The use of benzodiazepines should be avoided. There are other safer pharmacological alternatives. Benzodiazepine withdrawal may play a role in the occurrence of delirium in the elderly. Other withdrawal symptoms include tremor, agitation, insomnia and seizures (Turnheim 2003). Thus, when there is long-term use of benzodiazepines abrupt discontinuation might be difficult. Discontinuation should however not be withheld but done slowly and step-wise. If benzodiazepines are used in the elderly, short-acting benzodiazepines such as oxazepam are preferred, because they do not accumulate in the elderly to the same extent (Kompoliti and Goetz 1998). If short-acting benzodiazepines are used they should be prescribed with caution, at low doses, and for short periods. As with all pharmacotherapy the effects should be evaluated. Benzodiazepines are sometimes used as a behavioural control. One should always ask if this use is for the benefit of staff or the benefit of the patient. The presence of staff may be sufficient for behavioural control. 

A therapeutic alternative for treatment of anxiety and depression is the use of 5-HT1A agonists. Azapirones comprise the major class of 5-HT1A agonists of which buspirone (Buspar [4]) is the only FDA-approved 5-HT1A selective agonist (relative to the other 13 serotonin receptor subtypes) for anxiety currently on the US market (Scheme 19.1). Buspirone has shown efficacy in randomized controlled trials of GAD for which it was approved [5-7]. Unlike benzodiazepines, buspirone is not addictive... 

Benzodiazepines offer several advantages over alternative treatments. They act quickly, can be dose-adjusted in an expeditious manner, and can be administered both in scheduled doses and on an as-needed basis. Despite their rapid action, however, one controlled study of clonazepam showed that some patients did not experience a satisfactory treatment response for 6-8 weeks. One important... 

Stevens JC, Pollack MH. Benzodiazepines in clinical practice consideration of their longterm use and alternative agents. J Clin Psychiatry 2005 66(Supplement 2) 21-27. 

Naloxone (Narcan). Naloxone, like naltrexone, is a potent opioid receptor blocker. Its primary use has been to reverse opiate toxicity after an overdose. However, some physicians have found it is also useful for a process known as rapid opiate detoxification. Although opiate withdrawal is not life threatening, it can be extremely unpleasant. Most opiate addicts are fearful of the withdrawal symptoms therefore, it usually requires a slow, deliberate detoxification to keep the withdrawal symptoms in check. Rapid opiate detoxification is an alternative approach that keeps the taper and detoxification as brief as possible. In this approach, naloxone is used in conjunction with general anesthesia or a nonopiate sedative such as the benzodiazepine mid-... 

Serotonin-boosting antidepressants or longer-acting benzodiazepines are also both suitable first-line treatments for APD. For APD patients who are also troubled by depression, an antidepressant is obviously preferable. We also prefer to use antidepressants rather than benzodiazepines to treat APD patients who have a history of substance abuse. The current data suggests that any of the SSRls as well as nefazodone, mirtazapine, and venlafaxine may be helpful. When these do not work, a MAOI is a reasonable alternative provided the patient is willing to commit to the dietary regimen. 

The full complement of anxiety syndromes including panic, generalized anxiety, obsessive-compulsiveness, and post-traumatic stress disorder can arise in the after-math of TBI. In fact, anxiety may be the most common neuropsychiatric complication of TBI. Anxiety appears to be most likely to arise when the injury occurs to the right side of the brain. The treatment alternatives for post-TBl anxiety parallel those used when treating anxiety disorders and include serotonin-boosting antidepressants, buspirone (Buspar), and the benzodiazepines (see Table 12.1). 

Antidepressants. In our experience, clinicians who are trying to manage the behavior of impulsive or aggressive patients too often overlook antidepressants. Antidepressants are often just as effective as anticonvulsants, antipsychotics, or benzodiazepines, especially when managing mild-to-moderate behavioral disturbances. Furthermore, antidepressants are generally easier to use and easier to tolerate than these alternatives. Once again, the SSRIs are best studied and so represent the favored first-line treatment for managing mild-to-moderate behavioral lability... 

When all else fails, the patient may need to switch to another medication. Serotonin-boosting antidepressants are a reasonable alternative to benzodiazepines for patients with anxiety disorders. Likewise, there are several options for the bipolar patient who cannot tolerate GABAergic medications. 

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