Benzodiazepines depressive side effects

A new benzodiazepine, RO 5-4556 (26), proved effective in treatment of anxiety, tension and depressions Side effects were minimal. Human mental and motor performance were not... 

Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,10 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.10 Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines. 

The most common side effects associated with benzodiazepine therapy include central nervous system (CNS) depressive effects (e.g., drowsiness, sedation, psychomotor... 

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. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

During the maintenance phase, treatment can be fine-tnned. If persistent side effects (especially EPS) are a problem, then the antipsychotic can be gradnally switched or conntermeasures snch as anticholinergic therapy can be taken. In addition, maintenance therapy is also an appropriate time to address the less dramatic bnt nonetheless tronblesome symptoms snch as a mood distnrbance. Antidepressants are often used to treat depressed mood in patients with schizophrenia. Likewise, benzodiazepines are commonly nsed with an antipsychotic to treat persistent yet subsyndromal anxiety in schizophrenia patients. 

Benzodiazepines with a short half-life are excreted more rapidly than benzodiazepines with a long half-life and hence the risk of severe withdrawal side-effects is higher. Withdrawal symptoms include anxiety, depression, insomnia, headache and hallucinations. 

A significant advantage of the benzodiazepines over other central nervous system depressants (e.g., the barbiturates) is that they possess a much greater separation between the dose that produces sleep and the dose that produces death. This increased margin of safety has been one of the major reasons benzodiazepines have largely replaced the barbiturates and other types of sedative-hypnotics in the treatment of anxiety and insomnia. In addition, benzodiazepine aclministration is associated with few side effects. 

Some patients may experience jitteriness, restlessness, muscle tension, and disturbed sleep. These side effects typically occur early in treatment, before the antidepressant effect. All patients should be informed of the possibility of these side effects and be reassured that if they develop, they tend to be transient. In patients with preexisting anxiety, therapy should be started at low doses, with subsequent titration as tolerated. If overstimulation occurs with this approach, it will be less likely to be severe enough to result in nonadherence with therapy. The short-term use of a benzodiazepine also may help the patient cope with overstimulation in the early stages of treatment until tolerance to this side effect occurs. Despite these common transient stimulating effects, SSRIs are clearly effective in patients with anxiety or agitated depression. Similarly, insomnia that commonly occurs early in treatment may be tolerable if the patient is reassured that the side effect will be transient. Symptomatic, short-term treatment with a hypnotic at bedtime is reasonable. 

Benzodiazepines are used as hypnotics because they have the ability to increase total sleep time. They demonstrate minimal cardiovascular effects, but do have the ability to increase heart rate and decrease cardiac output. Most CNS depressants, including the benzodiazepines, exhibit the ability to relax skeletal muscles. Clozapine, a dibenzodiazepine, is used in the treatment of schizophrenia. It has both sedative and antipsychotic actions, and is the only FDA-approved medication indicated for treatment-resistant schizophrenia, and for reducing the risk of suicidal behavior in patients with schizophrenia. This drug can have potentially life-threatening side effects, but appears to have no abuse potential and will not be considered further. 

Antidepressant drugs, however, might have direct anxiolytic effects. That is, certain antidepressants such as paroxetine (Paxil) or venlafaxine (Effexor) can help reduce anxiety independent of their effects on depression.1,47 These antidepressants have therefore been advocated as an alternative treatment for anxiety, especially for people who cannot tolerate the side effects of traditional anxiolytics, or who might be especially susceptible to the addictive properties of drugs like the benzodiazepines.1,9,46 Moreover, antidepressants such as paroxetine or venlafaxine are now considered effective as the primary treatment for several forms of anxiety, including generalized anxiety disorder, social phobia, and panic disorder.4,29,53 Antidepressants, either used alone or in combination with antianxiety drugs, have become an important component in the treatment of anxiety. 

Benzodiazepines act on the central nervous system by slowing it down, thereby causing sedation and muscle relaxation. Immediate physiologic effects include depressed heartbeat and breathing, and physical unsteadiness. Side effects include skin rashes, nausea, and dizziness. 

Zaleplon possesses several of the clinical characteristics of traditional benzodiazepines, including the potential for additive CNS depression when administered with alcohol or other CNS depressants, a low potential for abuse, and relative safety in overdose. Zaleplon exhibited sedative effects similar to those of the benzodiazepines, with a lower likelihood of such undesirable side effects as memory loss, interaction with alcohol, and abuse potential [22],... 

Insomnia is a common complaint in the elderly. As people age they require less sleep, and a variety of physical ailments to which the elderly are subject can cause a change in the sleep pattern (e.g. cerebral atherosclerosis, heart disease, decreased pulmonary function), as can depression. Providing sedative hypnotics are warranted, the judicious use of short half-life benzodiazepines such as temazepam, triazolam, oxazepam and alprazolam for a period not exceeding 1-2 months may be appropriate. Because of their side effects, there would appear to be little merit in using chloral hydrate or related drugs in the treatment of insomnia in the elderly. It should be noted that even benzodiazepines which have a relatively short half-life are likely to cause excessive day-time sedation. The side effects and dependence potential of the anxiolytics and sedative hypnotics have been covered elsewhere in this volume (Chapter 9). 

When medications are used, treatment is typically started with an SSRI. Responses may take weeks or months to occnr. For example, OCD tends to have a rather large latency period before a benefit is observed. Panic disorder and social phobia tend to respond sooner, although, like depression, the lag period is measured in weeks, not days. A notable exception is the group of benzodiazepines, which have an almost instantaneous antianxiety effect. However, their use is limited because of possible cognitive side effects and the potential for addiction in susceptible populations. 

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