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Biomedical subjects

B Adinoff

Publications and source records attributed to B Adinoff.

At least 19 recordsLinked to original sources
PubMed2001

Drug abuse and bipolar disorder: comorbidity or misdiagnosis?

Bipolar disorder is a common, severe and cyclic psychiatric illness. A strong association between alcohol dependence and bipolar disorder has been reported in numerous studies. The abuse of other drugs including cocaine, amphetamines, opiates, cannabis, and prescription medications in bipolar patients is also an important public health concern and has been less extensively investigated. This review examines the abuse of drugs other than alcohol or nicotine in people with bipolar disorder. The high rates of milder affective symptoms but not mania observed in patients in drug abuse treatment settings suggests the symptoms may in many cases be associated with the drug use. However, such patients presenting in psychiatric settings might be suffering from cyclothymic and related attenuated bipolar disorders (type II). Substance abuse may be associated with medication non-compliance, more mixed or dysphoric mania and possibly an earlier onset of affective symptoms and more hospitalizations. The pharmacotherapy of patients with bipolar disorder and drug abuse is examined, including evidence on the use of mood stabilizers, neuroleptics and the newer atypical antipsychotics in this population.

Bipolar Disorder↗
PubMed2001

Limbic responsiveness to procaine in cocaine-addicted subjects.

OBJECTIVE: The limbic system plays a critical role in motivation, emotional expression, and memory. The authors investigated whether a state of permanent limbic neuronal hyperexcitability, or sensitization, is present in cocaine addicts as a consequence of repeated cocaine use. METHOD: Single photon emission computed tomography (SPECT) of regional cerebral blood flow (rCBF) was used to compare the central nervous system response to the limbic stimulus procaine in 10 cocaine-dependent male patients and 10 healthy comparison male subjects. RESULTS: The cocaine-addicted subjects demonstrated bilateral activation of the orbitofrontal cortex after the procaine challenge, whereas the comparison subjects showed activation of the anterior cingulate, bilateral insular, and right amygdalar regions. After receiving placebo, the cocaine-addicted subjects showed markedly lower rCBF in the bilateral orbitofrontal cortex than the comparison subjects. CONCLUSIONS: The pattern of hypoperfusion in the placebo state followed by heightened activation with procaine in the cocaine-addicted subjects is similar to the pattern of interictal hypoperfusion and ictal hyperperfusion that has been observed in subjects with epilepsy. The findings for the cocaine-addicted subjects may thus represent evidence of localized (orbitofrontal) sensitization.

Adult↗
PubMed2000

Comprehensive review of the psychiatric uses of valproate.

The therapeutic effects of valproate in psychiatric conditions are most substantially recognized in bipolar disorder. However, this well-tolerated medication may be beneficial in the treatment of other mental illnesses. In this article, the authors comprehensively review studies of valproate as treatment for psychiatric conditions, including bipolar, depressive, anxiety, and psychotic disorders; alcohol withdrawal and dependence; tardive dyskinesia; agitation associated with dementia; and borderline personality disorder. Valproate shows the most promising efficacy in treating mood and anxiety disorders, with possible efficacy in the treatment of agitation and impulsive aggression, and less convincing therapeutic response in treating psychosis and alcohol withdrawal or dependence. The authors conclude with a brief summary of its mechanism of action and therapeutic spectrum.

Anticonvulsants↗
PubMed1998

Cocaine discrimination: relationship to local anesthetics and monoamine uptake inhibitors in C57BL/6 mice.

Although the discriminative properties of cocaine have been examined extensively in rats, and to a lesser extent in other species, there are currently no reports on cocaine discrimination by mice. In one of our experiments, C57BL/6 (C57) mice acquired cocaine discrimination (10 mg/kg training dose) and exhibited dose responsive generalization to lower doses of the drug, which was similar to previous reports using rats. In addition, mazindol, a general monoamine uptake inhibitor similar to cocaine, and nomifensine, which is relatively specific for the dopamine transporter, substituted completely for cocaine, as described for rats. In contrast, there was little substitution evidenced by monoamine uptake inhibitors relatively specific for the norepinephrine transporter (nisoxetine) or for the serotonin transporter (fluoxetine), or by the local anesthetics procaine or lidocaine. In our second experiment, neither cocaine nor mazindol substituted for procaine in animals trained to discriminate the local anesthetic (100 mg/kg) although lidocaine substituted completely for the procaine cue. These experiments emphasize the importance of the dopamine transporter in mediating the discriminative stimulus effects of cocaine in C57 mice. The lack of cross generalization between cocaine and procaine suggests that the anesthetic properties of cocaine contribute little toward its discrimination by this mouse strain.

Anesthetics, Local↗
PubMed1998

Disturbances of the stress response: the role of the HPA axis during alcohol withdrawal and abstinence.

Interactions among the brain, the pituitary gland, and the adrenal glands (i.e., the hypothalamic-pituitary-adrenal [HPA] axis) help regulate the body's response to stress. The adrenal hormone cortisol plays a key role in stress reduction through its effects on multiple body systems. Excessive cortisol activity during both chronic alcohol administration and withdrawal may underlie some of the clinical complications of alcoholism, including increased risk of infectious diseases; bone, muscle, and reproductive system changes; altered energy metabolism; and disorders of mood and intellect. Despite excessive cortisol levels during intoxication and withdrawal, however, the HPA axis becomes less responsive to stress during abstinence, potentially resulting in an impaired capacity to cope with relapse-inducing stressors.

Ethanol↗
PubMed1997

Plasma gamma-aminobutyric acid (GABA) predicts outcome in patients with alcohol dependence.

1. Previous studies have suggested that low plasma GABA levels (< or = 100 pmol/ml) may characterize a subset of patients with alcohol dependence. 2. In order to assess the clinical relevance of this biologic finding, the authors followed 49 alcohol dependent patients for up to 18 months following inpatient treatment. Treatment outcome was assessed by continuous abstinence and continued contact with research personnel. 3. Alcohol dependent patients with low plasma GABA had significantly better outcome than patients with plasma GABA in the normal control range (101-150 pmol/ml). 4. These findings suggest that plasma GABA measures may prove to be clinically useful in identifying alcohol dependent patients at risk for relapse.

Alcoholism↗
PubMed1997

Dexamethasone in the treatment of the alcohol withdrawal syndrome.

Pre-clinical studies and clinical case reports suggest that glucocorticoids may be efficacious in ameliorating the signs and symptoms of the alcohol withdrawal syndrome. In order to evaluate the efficacy of the glucocorticoid dexamethasone upon alcohol withdrawal, we administered 4 mg of dexamethasone intravenously to eight alcohol dependent men during withdrawal. Withdrawal severity, as determined by the amount of lorazepam required to ameliorate withdrawal symptoms, was compared to eight other withdrawing patients not administered dexamethasone. There was no significant difference between the two groups in the amount of lorazepam required to treat to withdrawal symptoms. This preliminary study suggests that dexamethasone, in doses expected to suppress hypothalmic-pituitary-adrenal axis activation, is not efficacious in the treatment of alcohol withdrawal.

Adult↗
PubMed1996

Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence.

The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxietylike symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may, at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neuropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF.

Adult↗
PubMed1995

Levels of gamma-aminobutyric acid in cerebrospinal fluid and plasma during alcohol withdrawal.

Aminobutyric acid (GABA) is implicated in the biochemical pathophysiology of alcohol intoxication, dependence and withdrawal. We therefore measured GABA in both cerebrospinal fluid (CSF) and plasma from 14 male alcohol-dependent patients during acute alcohol withdrawal (day 1) and again after 21 days of inpatient treatment (day 21). Plasma GABA levels on admission correlated with indices of liver function. When corrected for differences in liver function, plasma levels of GABA levels on day 1 were significantly higher than on day 21. CSF GABA concentrations were also significantly higher during withdrawal compared with concentrations after 3 weeks of abstinence. The change in plasma GABA levels correlated significantly with the change in CSF GABA levels, although there was no correlation between plasma and CSF levels at either time. These findings demonstrate that changes in CSF GABA may be reflected in plasma GABA, and they highlight the potential importance of the GABA system in alcohol dependence and withdrawal.

Adult↗
PubMed1995

Features of cocaine dependence with concurrent alcohol abuse.

In order to assess differences between cocaine dependence alone and cocaine dependence complicated by alcohol abuse, 34 subjects who met DSM-III-R criteria for alcohol abuse and cocaine dependence (COC-ETOH group) were compared with 39 subjects who met criteria for cocaine dependence only (COC-only group) with regard to demographics, substance use, and psychopathology. There were no differences between groups in age, race, employment or socio-economic status. The baseline depression and global severity scores in the COC-ETOH group were significantly higher than in the COC-only group. The COC-ETOH group was significantly more likely to experience a paranoid psychosis with cocaine use and significantly more likely to have abused additional substances in the month prior to study entry. The COC-ETOH group also attended significantly fewer medication management sessions during the 12-week trial. There were no differences between groups in the type or frequency of Axis 1 or Axis II disorders.

Adult↗
PubMed1995

Fluvoxamine treatment of alcoholic amnestic disorder.

The serotonin uptake inhibitor fluvoxamine was assessed in treatment of alcohol-induced Korsakoff's syndrome (KS) using fixed (4 weeks, 200 mg/day) or individualized (6 weeks, plasma concentration > or = 400 ng/ml) dosing in randomized placebo-controlled double-blind crossover studies. Cognitive functions and concentrations of the major cerebrospinal fluid (CSF) metabolites of serotonin (5-HIAA), norepinephrine (MHPG), and dopamine (HVA) were determined in abstinent, nondepressed KS patients (aged 45-75), at baseline and placebo (3-4 weeks), and after 3-4 (n = 10) or 6 (n = 4) weeks of fluvoxamine administration. Fluvoxamine decreased CSF 5-HIAA compared to placebo (P < 0.003) without consistent changes in HVA or MHPG. Reductions in 5-HIAA correlated with improvements on the Wechsler Memory Scale Memory Quotient (P < 0.05), independent of effects on attention/vigilance or Beck Depression Inventory scores. Reductions in 5-HIAA correlated with plasma fluvoxamine (P < 0.03) only for fluvoxamine concentrations below 450 ng/ml. These findings suggest improvement of memory consolidation and/or retrieval in patients with Korsakoff's syndrome by fluvoxamine via serotonergic mechanisms.

Aged↗
PubMed1994

Double-blind study of alprazolam, diazepam, clonidine, and placebo in the alcohol withdrawal syndrome: preliminary findings.

Both a reduction in the inhibitory effects of GABA (disinhibition) and activation of the sympathetic nervous system are manifested during the alcohol withdrawal syndrome. This study was designed to explore the relative efficacy of medications that differentially affects these two biological systems: the benzodiazepines, which attenuate GABAergic disinhibition, and the alpha 2-adrenergic receptor agonists, which decrease sympathetic activation. The benzodiazepine diazepam (n = 6), the alpha 2-receptor agonist clonidine (n = 7), the benzodiazepine alprazolam (this is also purported to have alpha 2-receptor agonist properties) (n = 6), and placebo (n = 6) were evaluated in their effectiveness in decreasing signs and symptoms of alcohol withdrawal. Drug-free, alcohol-dependent patients were administered 1 of the 4 medications in a double-blind design until symptoms of withdrawal, as measured by the Clinical Instrument Withdrawal Assessment for Alcohol-Revised, were successfully treated. Alprazolam was significantly more efficacious than both clonidine and placebo in decreasing withdrawal symptoms. Diazepam was more effective than clonidine and placebo on some measures of withdrawal. Clonidine decreased systolic blood pressure significantly more than the other two active drugs and placebo, but was no more effective than placebo in decreasing other symptoms of withdrawal. Alprazolam did not significantly decrease blood pressure compared with diazepam or placebo. Despite the small sample size, these preliminary findings suggest that the efficacy of alprazolam in the treatment of alcohol withdrawal is related to its effect at the benzodiazepine receptor and not its alpha 2-receptor agonist properties.

Adult↗
PubMed1992

Vagal tone decreases following intravenous diazepam.

To investigate the relationship between anxiety and parasympathetic nervous system activity, cardiac vagal tone was assessed in six healthy volunteers after the intravenous administration of the anxiolytic diazepam. Vagal tone was determined by quantifying the amplitude of respiratory sinus arrhythmia. We observed a significant dose-dependent attenuation in vagal tone, accompanied by an increase in heart rate. There was a nonstatistically significant decrease in plasma norepinephrine concentrations and subjective anxiety ratings at higher doses of diazepam. We discuss a possible role of the parasympathetic nervous system in the anxiolytic effects of the benzodiazepines.

Adult↗