fluvoxamine and Substance-Related-Disorders

Medication treatment studies have demonstrated short-term efficacy of various SRIs, opioid antagonists, and mood stabilizers in sub-samples of adult treatment seeking pathological gamblers. Pathological gambling is frequently comorbid with bipolar spectrum disorders, substance abuse/dependence, and attention-deficit/hyperactivity disorder (ADHD), and comorbidity may influence treatment response in pathological gambling. This review focuses on recent research examining the treatment of pathological gambling and highlights methodological challenges for future studies.

Topics: Antidepressive Agents, Second-Generation; Behavior, Addictive; Bupropion; Comorbidity; Disruptive, Impulse Control, and Conduct Disorders; Dose-Response Relationship, Drug; Fluvoxamine; Gambling; Humans; Naltrexone; Outcome Assessment, Health Care; Paroxetine; Piperazines; Research Design; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders; Triazoles

Pathological gambling is a disabling disorder that affects at least 2 1/2 million Americans and their families. Although pathological gambling has been characterized as an impulse control disorder, it has also been associated with compulsivity. Essential features of pathological gambling include constantly recurring gambling behavior that is maladaptive, in that personal, familial, and/or vocational endeavors are disrupted. Affective disorders and substance abuse often co-occur. Incidence of suicidality is extremely high. Despite the fact that this disorder is a widespread public health problem, few controlled studies of causes or treatment have been conducted. Preliminary neurobiological studies implicate serotonergic dysfunction in pathological gamblers. Treatment with serotonin reuptake inhibitors, such as clomipramine and fluvoxamine, may be effective in treating this disorder. Well-defined and controlled clinical trials in large samples of pathological gamblers are needed.

Topics: Adolescent; Adult; Comorbidity; Compulsive Behavior; Disruptive, Impulse Control, and Conduct Disorders; Female; Fluvoxamine; Gambling; Humans; Lithium Carbonate; Male; Middle Aged; Mood Disorders; Obsessive-Compulsive Disorder; Placebo Effect; Psychotherapy; Selective Serotonin Reuptake Inhibitors; Self-Help Groups; Serotonin; Substance-Related Disorders; Treatment Outcome

Six and seven addicts treated with racemic methadone (MTD) were comedicated with fluvoxamine (FLV) and fluoxetine (FLX), respectively. The plasma concentrations of both (R)- (the active enantiomer) and (S)-MTD were increased by FLV, whereas only (R)-MTD concentrations were increased by the addition of FLX. This suggests that cytochrome P450IID6 (CYP2D6), an enzyme that is strongly inhibited by FLX, preferentially metabolizes (R)-MTD, whereas CYP1A2, which is strongly inhibited by FLV, metabolizes both enantiomers. The choice of a selective serotonin reuptake inhibitor in depressive addicted patients treated with MTD and the possible use of FLX or FLV to potentiate the effects of MTD in some cases of therapeutic failure are discussed.

Topics: Fluoxetine; Fluvoxamine; Humans; Methadone; Narcotics; Selective Serotonin Reuptake Inhibitors; Statistics, Nonparametric; Stereoisomerism; Substance-Related Disorders

The chronic effects of fluvoxamine (200 mg per day for 4 weeks) were studied in ten alcoholic organic brain syndrome patients in a double-blind cross-over design. Complete neuropsychological evaluation was performed as well as measurement of neurochemical changes in CSF. Fluvoxamine produced a small but significant improvement in memory performance. An analysis of fluvoxamine minus placebo difference scores showed a significant correlation between memory functioning and CSF 5HIAA levels. Alcohol amnestic syndrome patients who had the highest blood levels of fluvoxamine demonstrated the largest changes in CSF 5HIAA and improvement in memory performance under fluvoxamine. These findings implicate a role of serotonergic mechanisms in alcoholic organic brain syndrome and suggest that with individual titration of the drug dose, fluvoxamine might be a clinically useful agent in the treatment of this syndrome.

Topics: Aged; Alcohol Amnestic Disorder; Dementia; Double-Blind Method; Ethanol; Fluvoxamine; Humans; Hydroxyindoleacetic Acid; Middle Aged; Oximes; Substance-Related Disorders

Dysfunction of monoamine neurotransmission seems to contribute to such pathopsychological states as depression, schizophrenia, and drug abuse. The present study examined the effects of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and antidepressant fluvoxamine on locomotor activity in rats following administration of the catecholamine reuptake inhibitor mazindol. Mazindol (1 mg/kg) did not alter locomotor activity; whereas, fluvoxamine (20 mg/kg) given alone induced a brief period of hypomotility. Hyperactivity was elicited in a dose-related manner when fluvoxamine (5-20 mg/kg) was combined with mazindol (1 mg/kg). The hyperactivity elicited by fluvoxamine (20 mg/kg) plus mazindol (1 mg/kg) was significantly attenuated by the 5-HT(2A) receptor antagonist M100907 (2 mg/kg) and potentiated by the 5-HT(2B/2C) receptor antagonist SB 206553 (2 mg/kg). Neither antagonist significantly altered basal activity. The hyperactivity evoked by the combination of fluvoxamine and mazindol seems to be mediated in part by 5-HT(2A) receptors; whereas, 5-HT(2B/2C) receptors may serve to limit this effect. Thus, the balance of activation between 5-HT(2A) and 5-HT(2B/2C) receptors seems to contribute to the expression of locomotor hyperactivity evoked via combination of a 5-HT and a catecholamine reuptake inhibitor. A disruption in this balance may contribute to the expression of affective disorders, schizophrenia, and drug abuse.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Biogenic Monoamines; Catecholamines; Depression; Dopamine; Drug Synergism; Fluorobenzenes; Fluvoxamine; Indoles; Male; Mazindol; Motor Activity; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2B; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Schizophrenia; Selective Serotonin Reuptake Inhibitors; Serotonin; Substance-Related Disorders

The aim of this paper is to report a case of symptomatic methadone toxicity associated with fluvoxamine treatment.. A 28-year-old woman was admitted to hospital with severe hypoxaemia and hypercapnia indicating hypoventilation. Medication prior to admission had been stable and included methadone 70 mg daily and diazepam 2 mg twice daily. Three weeks before admission she had commenced treatment with fluvoxamine.. Methadone was decreased to 50 mg daily and diazepam was tapered to zero.. The serum methadone concentration decreased and oxygenation improved considerably.. Clinicians should be aware of the potential for a significant drug interaction between fluvoxamine and methadone.

Topics: Adult; Antidepressive Agents, Second-Generation; Depressive Disorder; Drug Interactions; Female; Fluvoxamine; Humans; Hypercapnia; Hypoxia; Methadone; Narcotics; Substance-Related Disorders

We report nine cases where fluoxetine (FX) (20 mg/day) was added to maintenance treatment with methadone (MTD) (dose range: 30-100 mg) in addicts with affective disorders. MTD plasma levels were measured before and after treatment with FX under steady-state conditions. Among the nine patients, two also received fluvoxamine (FLVX) at different times. Although it is possible that in some patients a moderate FX-MTD interaction occurs, resulting in increased plasma levels of MTD, this interaction is certainly less marked than that between FLVX and MTD and unlikely to have clinical consequences.

Topics: Adult; Analgesics, Opioid; Antidepressive Agents, Second-Generation; Drug Interactions; Female; Fluoxetine; Fluvoxamine; Humans; Male; Methadone; Mood Disorders; Selective Serotonin Reuptake Inhibitors; Substance-Related Disorders

The acute and chronic effects of paroxetine and fluvoxamine on naloxone withdrawal-induced place aversion in morphine dependent rats were investigated. Acutely administered fluvoxamine (25 mg/kg s.c. given 30 min prior to naloxone withdrawal pairing) and chronic daily paroxetine (10 mg/kg s.c.) coadministration with a morphine induction protocol, both attenuated morphine withdrawal place aversion. Conversely, acutely administered paroxetine (up to 25 mg/kg s.c.) or chronic daily fluvoxamine (10 mg/kg s.c.) coadministration with morphine did not modify subsequent withdrawal place aversion. Previous radioligand binding studies indicate that fluvoxamine has opioid-displacing properties. It is suggested therefore that acute fluvoxamine may have decreased withdrawal aversion, probably through serotonin and also, in part, via an opioid-like mechanism whereas chronic paroxetine decreased withdrawal aversion by a serotonergic mechanism, but it is not clear whether opioid systems play any role in the action of paroxetine.

Topics: Analysis of Variance; Animals; Conditioning, Psychological; Disease Models, Animal; Drug Administration Schedule; Fluvoxamine; Injections, Subcutaneous; Male; Morphine; Naloxone; Paroxetine; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Serotonin; Substance Withdrawal Syndrome; Substance-Related Disorders