Antidepressants physical dependence

The pharmacoeconomics of the anxiety disorders has received litde attention. In the past drug costs were largely incurred by use of benzodiazepines, most of which are available in generic forms and are cheap. They are effective and acceptable in the short term. Long-term use is associated with the risk of physical dependence, with an adverse risk—benefit ratio and high cost terms to facilitate withdrawal. There is now a trend towards the use of antidepressants in the anxiety disorders. Clinical experience has been followed by formal trial evaluation. 

Fluniazenil is not indicated in all cases of suspected BZ overdose, and it is contraindicated when cyclic antidepressant involvement is known or suspected because of the risk of seizures. It should be used with caution when BZ physical dependence is suspected, as it may precipitate BZ withdrawal. 

Several natural products have been evaluated in rodent models of nicotine withdrawal. An extract of Hypericum perforatum (St. John s Wort, a putative antidepressant, and inhibitor of serotonin reuptake) reversed somatically expressed withdrawal behaviors and locomotor depression in spontaneous withdrawal (Catania et al. 2003). A benzoflavone compound isolated from Passiflora incarnata, interfered with the induction of physical dependence. Coadministration with chronic nicotine prevented various subsequent indicators of withdrawal syndrome in the mouse, including jumping, locomotor inactivity, immobility in the swim test and naloxone-precipitated escape jumping (Dhawan et al. 2002). 

In order to increase the external validity of our models, it might be desirable to consider some nonnicotine ingredients of tobacco smoke. It appears that there are natural monamine oxidase (MAO) inhibitors in tobacco smoke (Lewis et al. 2007). It would be interesting to determine whether the coadministration of a low dose of a standard MAO inhibitor along with chronic nicotine would increase physical dependence, as assessed by various withdrawal measures, hi view of the antidepressant properties of MAO inhibitors, measures reflecting aspects of depression might be particularly affected. 

Azapirones. Though several azapirones have been developed and tested in the laboratory setting, only one, bnspirone (Bnspar), is currently on the market. Buspirone is the first nonsedating, nonbenzodiazepine anxiolytic, other than the antidepressants described earlier. It has no dependence or addictive liability and is not lethal in overdose. Buspirone is also devoid of many of the problems of the benzodiazepines such as sedation, motor impairment, addiction, physical dependence, or withdrawal. Yet, doubts remain in the minds of many practitioners regarding the effectiveness of buspirone. This will be discussed in more detail later in this chapter. 

Most of the research and results have been focused on the effects of drug therapy on the disorders induced by alcohol, and by opiates abuse. For all drugs, the first objective is to wean the patients from the drug, treating or preventing the effects of withdrawal for those drugs which cause physical dependence (alcohol, nicotine, opiates, caffeine, certain psychotropic agents such as benzodiazepines, possibly antidepressants). The second phase is the prevention of recurrence or relapse, which relies on a com-... 

On cessation, treatment should be tapered slowly. A proportion of patients have significant withdrawal symptoms to antidepressants on tapering that respond to the reinstitution of treatment. At present there is no known treatment for the physical dependence linked to antidepressants when severe other than gradual tapering. 

Answer B. Buspirone has selective anxiolytic activity that is slow in onset The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Baclofen is a spinal cord muscle relaxant that activates GABAfi receptors. Buprenorphine is a long-acting opioid analgesic with no effectiveness in GAD, and butabarbital is a barbiturate that may cause dependence. 

TOLERANCE AND PHYSICAL DEPENDENCE Some tolerance to the sedative and autonomic effects of tricyclic antidepressants and to the nausea commonly associated with SSRls... 

Because long-term exposure to high-dose benzodiazepines may place some patients at risk for physical and psychological dependence, we recommend the use of antidepressants for the treatment of panic disorder. For most patients, SSRIs should be considered first-line agents. The choice should be based on the factors discussed in Chapter 2. MAOls are usually reserved for patients whose symptoms have not responded to SSRIs and TCAs. A major caveat is that patients with panic disorder initially may be highly sensitive to the stimulant effect of small doses of antidepressants. For highly anxious patients with panic disorder, treatment may be... 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

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