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The cause of prolonged or recurrent symptoms following the cessation of long-term benzodiazepine use is proposed to be related to downregulation and allosteric decoupling of the γ-aminobutyric acid/benzodiazepine receptor complex. This case series describes 2 patients with prolonged (>2 weeks) recurrent complications during attempted tapering of benzodiazepine doses after long-term treatment. Excited catatonia developed in a 90-year-old woman, and prolonged delirium developed in a 69-year-old woman. Both patients showed improvement of symptoms after resumption of higher doses of benzodiazepine treatment and recurrence of symptoms when the dose was again lowered. Caution should be exercised regarding the long-term use of benzodiazepines in older adults (aged ≥65 years). Tapering of benzodiazepines in older patients after long-term treatment may require slow decreases in dose over long periods. Psychotherapeutic interventions, such as brief cognitive therapy with psychoeducation and motivational enhancement, and osteopathic manipulative treatment to decrease paravertebral muscle tension may be beneficial during the tapering process.

Carisoprodol (N-isopropyl-2 methyl-2-propyl-1,3-propanediol dicarbamate; N-isopropylmeprobamate) is a centrally acting skeletal muscle relaxant whose primary active metabolite is meprobamate, a substance with well established abuse potential similar to that of benzodiazepines. A number of reports show that carisoprodol has been abused for its sedative and relaxant effects, to augment or alter the effects of other drugs, and by the intentional combination of carisoprodol and other noncontrolled medications because of the relative ease (as compared to controlled substances) of obtaining prescriptions. The diversion and abuse of carisoprodol and its adverse health effects appear to have dramatically increased over the last several years. Clinicians have begun to see a withdrawal syndrome consisting of insomnia, vomiting, tremors, muscle twitching, anxiety, and ataxia in patients who abruptly cease intake of large doses of carisoprodol. Hallucinations and delusions may also occur. The withdrawal symptoms are very similar to those previously described for meprobamate withdrawal, suggesting that what may actually be occurring is withdrawal from meprobamate accumulated as a result of intake of excessive amounts of carisoprodol. However carisoprodol itself is capable of modulating GABA(A) function, and this may contribute both to the drugs abuse potential and to the occurrence of a withdrawal syndrome with abrupt cessation of intake. Carisoprodol has been classified as a controlled substance in several states in the US and restrictions on the use of the drug have been imposed in some European countries. Carisoprodol is metabolized to a controlled substance, has clear evidence of abuse potential and increasing incidence of abuse, and has shown evidence of a withdrawal syndrome with abrupt cessation from intake. This article will discuss the abuse potential of carisoprodol and the associated withdrawal syndrome, and consider implications for future use of the drug.

Carisoprodol is a commonly used centrally acting muscle relaxant. A number of case reports have suggested that the drug may have abuse potential, presumably because it is metabolized to the anxiolytic drug, meprobamate, which is a controlled substance at the federal level. Two recent case reports described symptoms of withdrawal after the cessation of carisoprodol. We present two additional cases that support the concept of a withdrawal syndrome with this drug. Symptoms of carisoprodol withdrawal include anxiety, tremulousness, insomnia, jitteriness, muscle twitching, and hallucinations. These symptoms are most likely caused by withdrawal from the meprobamate that accumulates after large amounts of carisoprodol are ingested. Although carisoprodol is not a controlled substance at the federal level, clinicians should be aware of its significant potential for abuse.

A 43-year-old man with chronic back and shoulder pain was treated with hydrocodone. He began taking excessive amounts of the drug, so his physicians stopped prescribing it. The patient then obtained the muscle relaxant carisoprodol on his own from several sources. He was consuming up to 30 or more tablets/day (> or =10,500 mg/day) for several weeks, then abruptly stopped taking the drug. Within 48 hours he developed anxiety, tremors, muscle twitching, insomnia, auditory and visual hallucinations, and bizarre behavior. The symptoms intensified and peaked on the fourth day after carisoprodol cessation. The patient required brief treatment with olanzapine and tapering dosages of lorazepam while the symptoms gradually resolved. To our knowledge, this is the first documented case of a withdrawal syndrome with carisoprodol. The symptoms most likely resulted because of accumulation of meprobamate, the active metabolite of carisoprodol in humans. Clinicians prescribing carisoprodol should be aware of the possibility for abuse or addiction. Further, we recommend that carisoprodol be designated a controlled substance at the federal level.

Electric shock-like sensations may occur after cessation of treatment with serotonin selective reuptake inhibitors but are reported in the literature only rarely with discontinuation of venlafaxine. Two patients experienced severe shock-like sensations during venlafaxine withdrawal. For both patients symptoms occurred with lowering of the dosage and persisted for 5 days after complete discontinuation of the drug. These sensations may represent significant alteration of neuronal activity in the central nervous system.

Carisoprodol is a commonly used skeletal muscle relaxant with potential for abuse because of its active metabolite, meprobamate, and several reports have suggested that patients abruptly stopping intake of carisoprodol may have a withdrawal syndrome. The authors studied changes in the occurrence of somatic dysfunctions in five patients during an 8-day period following discontinuation from large doses of carisoprodol. Results showed that the number of somatic dysfunctions changed significantly during the withdrawal period. Each patient had an increase in the number of somatic dysfunctions during the first 3 days after cessation of carisoprodol with return to at or near baseline by the eighth day. This was reflected statistically in a significant-within-subjects effect for time. Results of supplemental analyses revealed a significant component of the effect and a trend for the quadratic component to be significant. Increases in the number of somatic dysfunctions during carisoprodol discontinuation support the existence of a carisoprodol withdrawal syndrome.

Most previous studies of the neurophysiological effects of caffeine have focused on the effects of caffeine ingestion, and few studies have examined the effects of caffeine withdrawal. This open study evaluated the quantitative EEG (QEEG) changes occurring during a 4-day period of abstinence in subjects who habitually consume 300 mg or more of caffeine daily. Thirteen subjects underwent QEEG studies during their usual caffeine consumption (baseline) and on days 1, 2, and 4 of a 4-day period of caffeine abstinence. Ten of the subjects underwent a second QEEG on day 4 that consisted of a period of recording after reinstitution of caffeine. A comprehensive analysis of multiple quantitative variables was performed for each study during the abstinence period and compared to the variables obtained at baseline for each subject. Changes occurring during caffeine abstinence included: 1) increases in theta absolute power over all cortical areas, 2) increases in delta absolute power over the frontal cortex, 3) decreases in the mean frequency of both the alpha and beta rhythm, 4) increase in theta relative power and decrease in beta relative power, and 5) significant changes in interhemispheric coherence. Most of these changes tended to return to pre-abstinence baseline levels rapidly after resumption of caffeine consumption. The caffeine withdrawal state affects a number of neurophysiological variables. Further investigation of the neurophysiological aspects of caffeine withdrawal using placebo controlled double blind assessment methods is warranted.

Auditory and visual P300 cognitive evoked potentials were obtained in 13 individuals who regularly consumed caffeine prior to and during a 4 day period of abstinence from caffeine. During the period of caffeine abstinence auditory P300 evoked potentials showed significant decreases in amplitude measures but no significant changes in latency, while the visual P300 evoked potentials showed significant latency decreases but no significant changes in amplitude. The reason for these opposite effects is unclear and further research in this area is needed.

Carisoprodol (Soma) is a noncontrolled, skeletal-muscle relaxant whose active metabolite is meprobamate. Despite previous indications that the drug may be abused, it continues to be widely prescribed for musculoskeletal conditions involving muscle spasm. Presented here are three cases demonstrating patterns of carisoprodol abuse not previously reported. Carisoprodol usage should be limited to short-term treatment. Patients for whom carisoprodol is prescribed are at risk for meprobamate dependence.

The authors studied the effects of caffeine withdrawal on 14 subjects at baseline and during a 4-day period of abstinence from caffeine. They studied the results from quantitative electroencephalograms performed on these subjects and gauged any changes that may have been evoked during this withdrawal period. The participants were also evaluated for the occurrence of somatic dysfunctions. Examinations for the presence of somatic dysfunctions were performed on the participants before caffeine cessation and on Days 1, 2 and 4 of abstinence. Results showed that the number of somatic dysfunctions increased significantly during the process of caffeine withdrawal.

As part of a quantitative EEG study of caffeine withdrawal a serendipitous observation suggested that individuals with Diffuse Paroxysmal Slowing (a minor EEG dysrhythmia) in their baseline resting EEGs had an increased firing rate of this pattern while undergoing a period of caffeine abstinence. For all EEGs, individual bursts of Diffuse Paroxysmal Slowing were identified by consensus rating and the firing rate for this pattern expressed as the number of bursts per 10 minutes of alert waking activity. The firing rate of this pattern was seen to increase markedly during 4 days of verified abstinence and to return to baseline or lower than baseline levels following reintroduction of caffeine. Some possible implications of this phenomenon are discussed.

Neurophysiological consequences of withdrawal from caffeine are poorly understood. In particular, quantitative studies of EEG changes that may occur during the period of caffeine abstinence in caffeine dependent individuals have not been reported. In this pilot study, 13 physically- and psychiatrically-normal caffeine users were asked to abstain from caffeine for a period of 4 days. Quantitative EEGs were obtained prior to stopping caffeine and on Days 1, 2, and 4 of the caffeine abstinence period. Results indicated that significant increases in alpha and theta absolute power accompany the caffeine withdrawal process with return to the pre-abstinent EEG levels when caffeine usage is resumed. The implications of these findings are discussed with special reference to the possible need to control for the variable of caffeine usage in quantitative EEG studies of other phenomena.