Benzodiazepines depression from

The benzodiazepines such as diazepam, oxazepam, and temazepam are common causes of acute poisoning, but rarely cause serious toxicity by themselves, even in enormous doses. They can potentiate central nervous system depression from other drugs, including alcohol. 

Although rare, benzodiazepine toxicity may occur from an overdose of the drug. Benzodiazepine toxicity causes sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote (antagonist) for benzodiazepine toxicity and acts to reverse die sedation, respiratory depression, and coma within 6 to 10 minutes after intravenous administration. The dosage is individualized based on the patient s response, widi most patients responding to doses of 0.6 to 1 mg. However, die drug s action is short, and additional doses may be needed. Adverse reactions of flumazenil include agitation, confusion, seizures, and in some cases, symptoms of benzodiazepine withdrawal. Adverse reactions of flumazenil related to the symptoms of benzodiazepine withdrawal are relieved by die administration of die benzodiazepine. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

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. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

When treating mild-to-moderate panic disorder, we recommend avoiding benzodiazepines in favor of CBT or antidepressants. Because CBT and antidepressants are both effective for panic disorder and major depression (commonly comorbid with panic disorder), the choice between the two largely rests on patient preference. Antidepressants are preferred for those who are pessimistic regarding the potential benefit of CBT, cannot afford CBT, or are unable (or unwilling) to invest the time necessary to complete a course of CBT. In our experience, some patients may accrue significant beneht from the combined treatment, particularly those with more moderate symptoms who struggle with the exposure aspects of therapy. 

The long-acting benzodiazepine clonazepam can be used as a first-line agent for those patients with particularly severe symptoms who are unable or unwilling to wait for the delayed therapeutic benefit of an antidepressant. Clonazepam can be initiated as a monotherapy for those without comorbid depression or in conjunction with an antidepressant for those who are also depressed. In the latter case, clonazepam can be used transiently with a plan to taper and discontinue it once sufficient time has elapsed to experience benefit from antidepressant therapy. 

Historically, the treatment of alcohol use disorders with medication has focused on the management of withdrawal from the alcohol. In recent years, medication has also been used in an attempt to prevent relapse in alcohol-dependent patients. The treatment of alcohol withdrawal, known as detoxification, by definition uses replacement medications that, like alcohol, act on the GABA receptor. These medications (i.e., barbiturates and benzodiazepines) are cross-tolerant with alcohol and therefore are useful for detoxification. By contrast, a wide variety of theoretical approaches have been used to reduce the likelihood of relapse. This includes aversion therapy and anticraving therapies using reward substitutes and interference approaches. Finally, medications to treat comorbid psychiatric illness, in particular, depression, have also been used in attempts to reduce the likelihood of relapse. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

Among ai-, a2- and as-point-mutated mice, only the ai(HlOlR) mutants were resistant to the depression of motor activity by diazepam and zolpidem (Rudolph et al. 1999 Low et al. 2000 Crestani et al. 2000). This effect was specific for ligands of the benzodiazepine site, since pentobarbital or a neurosteroid remained as effective in ai(HlOlR) mice as in wild-type mice in inducing sedation. An ai(HlOlR) mouse line was also generated by McKernan et al. (2000), confirming that sedation is finked to ai GABAa receptors and differs mechanistically from the anxiolytic action of benzodiazepines. 

The CNS depressants include barbiturates, nonbarbiturate sedatives, and the benzodiazepines. As the medical use of barbiturates decreased, primarily because of their high addiction liability and the danger of acute lethality, the use of the benzodiazepine anxiolytics increased. The most commonly abused barbiturates are secobarbital, pentobarbital, and amobarbital. Pheno-barbital is not generally abused, because of its slow onset of action. The most commonly abused anxiolytics include diazepam, chlordiazepoxide, midazolam, lo-razepam, and flurazepam. These drugs are readily attainable from illicit sources. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Mechanism of Action A benzodiazepine that enhances the action of the inhibitory neurotransmitter gamma-aminobutyric acid in the brain. Therapeutic Effect Produces sedative effect from its CNS depressant action. 

MecfMtiism of Action A BZ-1 receptor selective benzodiazepine with sedative properties. Therapeutic Effect Produces sedative effect from its central nervous system (CNS) depressant action. 

Goa and Ward 1986 Pecknold et al. 1989 Rickels et al. 1982]. In contradistinction to benzodiazepines, the therapeutic effect of buspirone has a lag period similar to that of antidepressants in depression, suggesting that its therapeutic benefits derive from receptor modulation. In addition, buspirone seems to act preferentially in those patients who are not responsive to benzodiazepines, suggesting a possible subgrouping of generalized anxiety disorders. 

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