Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concern about physical dependence seems to be the major limiting factor in the long-term treatment with benzodiazepines (BZD). The severity of the withdrawal syndrome is determined by multiple factors, e.g. dose, duration of use, frequency of dose interval, mode of discontinuation, the pharmacologic characteristics of the BZD, personality and previous or concurrent use of cross-dependent drugs and/or alcohol. There is evidence that BZD with a short elimination half-life cause a more severe withdrawal syndrome than those with a long elimination half-life. Besides pharmacokinetic properties, pharmacodynamic factors such as potency may also covary with the liability of a BZD to induce physical dependence. There is an increasing body of literature indicating that quickly eliminated, high potency BZD such as alprazolam and lorazepam may be more likely to cause severe withdrawal reactions than slowly eliminated compounds such as diazepam or less potent derivatives such as oxazepam. Alprazolam seems to play an exceptional role, insofar as relatively soon after its introduction to the market a number of case reports of withdrawal psychoses, seizures and intense rebound anxiety were published. Data reviewed from the literature correspond well with the results of interviews conducted with 31 clinicians across the United States with experience in detoxifying patients dependent on BZD, 84% of these physicians mentioning alprazolam as especially problematic with respect to the intensity and/or duration of the withdrawal syndrome.
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PMID:Physical dependence on benzodiazepines: differences within the class. 168 52

Alprazolam (48 mg/kg/day) administered orally to dogs 4 times a day in equally divided doses produced physical dependence. This dependence was revealed by a precipitated abstinence syndrome which occurred after either oral administration of flumazenil (6, 18 and 36 mg/kg) or intravenous administration of a liposomal suspension of flumazenil. Flumazenil alone (18, 36 and 72 mg/kg) produced no significant signs of precipitated abstinence in naive dogs. This precipitated abstinence syndrome in alprazolam-dependent dogs was characterized by both clonic and tonic-clonic seizures. Other signs of precipitated abstinence which comprise the NPAS score were less intense in the alprazolam-dependent than in diazepam-dependent dogs. Alprazolam is extensively metabolized in the dog and does not accumulate whereas its predominant metabolite, alpha hydroxyalprazolam, does accumulate. The data suggest that alpha hydroxyalprazolam plays a role in the dependence-producing properties of alprazolam in the dog as revealed by the precipitated abstinence syndrome.
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PMID:Dependence-producing properties of alprazolam in the dog. 211 Oct 29

This article compares panic disorder (PD) medications and discusses long-term therapy. In a review of the literature, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and benzodiazepines prove effective in treating PD. MAOIs treat comorbid depression; frequent side effects are dizziness and orthostatic hypotension. SSRIs are better tolerated than MAOIs, producing mild anticholinergic effects, but also producing gastrointestinal side effects and sexual dysfunction. Benzodiazepines are generally well tolerated when titrated gradually; moderate sedation is the most common short-term side effect. Long-term risks are physical dependence and withdrawal reactions. One hundred six PD patients were enrolled in a double-blind, 8-month, placebo-controlled trial of alprazolam and imipramine. In the 8-week short-term phase, daily dosages were titrated up to 10 mg/day of alprazolam and 250 mg/day of imipramine. The greatest number of dropouts occurred during this phase (lack of improvement and/or side effects). Alprazolam patients had a significantly more rapid onset of improvement and lower adverse events and attrition rates. In the 6-month maintenance period, patients continued short-term treatment. Patients receiving either alprazolam or imipramine developed tolerance to some side effects. At maintenance-phase completion, 62% of the alprazolam-group patients and 26% of both the imipramine- and placebo-group patients were panic free (p<0.01). Dosages were tapered to zero over 3 weeks; one third of the alprazolam patients could not discontinue. During the unblinded, 15-month follow-up, patients received open treatment selected by personal physicians on an as-needed basis. At the end of follow-up, all patients were reassessed. Patients who had completed both short-term and maintenance phases were far more likely to be panic-free (85% vs. 55%; p<0.01). PD is chronic and recurrent, and 8 months is an effective treatment period. Maintenance treatment does not lead to tolerance, even with benzodiazepines. Dose tapering must be very gradual. Completion of a long-term maintenance program strongly predicts remission.
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PMID:Panic disorder: long-term pharmacotherapy and discontinuation. 987 8