fluvoxamine and Substance-Withdrawal-Syndrome

Agomelatine (Valdoxan) is licensed by the European Medicines Agency for the treatment of major depressive episodes in adults. The objective of this review was to consider how the drug should be used in clinical practice in particular starting, stopping and switching to and from the drug.. The existing clinical evidence was reviewed.. Data suggest that when switching to agomelatine from other antidepressants consideration should be given to tapering the previous antidepressant in order to minimize the risk of the original drug causing discontinuation/withdrawal symptoms. The risk of pharmacological interactions between most antidepressants and agomelatine is low and so tapering the previous antidepressant can usually be done after agomelatine has been started. An exception is fluvoxamine which should not be concurrently prescribed with agomelatine. As agomelatine appears to cause no significant discontinuation symptoms, it can probably be stopped abruptly when treatment is completed or when switching to another antidepressant.. While this guidance may change as clinical evidence and experience grows, currently agomelatine appears to have a good tolerability profile and is relatively easy to use, though prescribers should note the requirement to conduct liver function tests (LFTs) in accordance with the Summary of Product Characteristics (SPC).

Topics: Acetamides; Animals; Antidepressive Agents; Contraindications; Depressive Disorder, Major; Drug Interactions; Drug Monitoring; Fluvoxamine; Humans; Liver; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Serotonin 5-HT2 Receptor Antagonists; Substance Withdrawal Syndrome

The discontinuation of many pharmacologic agents is associated with characteristic withdrawal symptoms. Antidepressants, particularly the tricyclic antidepressants (TCAs), are known to be associated with a group of common symptoms upon discontinuation. Serotonin reuptake inhibitors (SRIs) are also taking their respective place in the literature with reports of discontinuation symptoms. This review summarizes case reports and reports that allow systematic assessment of discontinuation symptoms following SRI discontinuation.. A computerized literature search was conducted using a MEDLINE search to identify reports of withdrawal effects following discontinuation of SRIs. Additional reports were found in the bibliographies of various published reports.. SRI discontinuation symptoms in adults are summarized in 24 case reports and 9 reports from controlled clinical trials. Additionally, 3 case reports addressing SRI discontinuation in the neonate are described. The reports describe clusters of symptoms commonly associated with the discontinuation of an SRI.. We propose to define an antidepressant discontinuation syndrome as the onset of a cluster of somatic and psychic symptoms following the discontinuation of an SRI and not attributable to other causes (e.g., concomitant medication, illness). These symptoms include dizziness, light-headedness, insomnia, fatigue, anxiety/agitation, nausea, headache, and sensory disturbance. The syndrome may last up to 3 weeks and may be improved by restarting the antidepressant or starting an antidepressant with a similar pharmacologic profile.

Topics: 1-Naphthylamine; Adolescent; Adult; Child; Clinical Trials as Topic; Cyclohexanols; Dizziness; Female; Fluoxetine; Fluvoxamine; Headache; Humans; Infant; Infant, Newborn; Male; MEDLINE; Mental Disorders; Middle Aged; Nausea; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sensation Disorders; Sertraline; Sleep Initiation and Maintenance Disorders; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride

Acute and chronic administration of the selective serotonin reuptake inhibitors (SSRIs) have been widely reported to disrupt sleep in laboratory studies. This study examines the naturalistic, longitudinal effects of paroxetine and fluvoxamine on sleep quality in the home setting.. Fourteen healthy volunteers free of medical and neuropsychiatric symptoms entered a 31-day protocol: 7 days of drug-free baseline (days 1-7), 19 days of drug treatment (steady state during days 18-26), and 5 days of acute withdrawal (days 27-31). On day 8, the subjects were randomly assigned to receive either 100 mg/day of fluvoxamine or 20 mg/day of paroxetine (half receiving each drug) in divided morning and evening oral doses. Investigators remained blinded to drug assignment until all sleep data had been analyzed. Sleep was monitored using the Nightcap ambulatory sleep monitor. Four standard and 3 novel measures were computed and compared using multivariate analysis of variance, analysis of variance, and Bonferroni-corrected comparison of means.. Sleep disruption was most clearly demonstrated using the novel measures eyelid quiescence index, rhythmicity, and eyelid movements per minute in non-rapid eye movement sleep, but was also apparent as determined by standard measures of sleep efficiency, number of awakenings, and sleep onset latency. Paroxetine disrupted sleep more than fluvoxamine, and paroxetine-induced sleep disruption persisted into the withdrawal phase. Rapid eye movement sleep was suppressed during treatment (especially for fluvoxamine) and rebounded during withdrawal (especially for paroxetine).. We confirm laboratory polysomnographic findings of SSRI-induced sleep quality changes and demonstrate the Nightcap's efficacy as an inexpensive longitudinal monitor for objective sleep changes induced by psychotropic medication.

Topics: Adult; Circadian Rhythm; Drug Administration Schedule; Equipment Design; Eyelids; Female; Fluvoxamine; Head; Humans; Longitudinal Studies; Male; Monitoring, Ambulatory; Monitoring, Physiologic; Movement; Paroxetine; Polysomnography; Selective Serotonin Reuptake Inhibitors; Sleep; Sleep Stages; Sleep, REM; Substance Withdrawal Syndrome

Recently, tricyclic antidepressants (TCAs) have been used mainly for treatment-resistant depression (TRD) because of their significant side effects . We report a patient whose prolonged depressive symptoms dramatically improved after the cessation of TCAs. TCAs may cause deterioration of depressive symptoms due to their neurotoxicity.

Topics: Adult; Antidepressive Agents, Tricyclic; Cabergoline; Depressive Disorder, Major; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Ergolines; Female; Fluvoxamine; Humans; Imipramine; Substance Withdrawal Syndrome; Treatment Outcome

Drug dependence is a social problem of over the world and resistant to medical intervention by psychiatrist as well as general clinicians. In Japan, methamphetamine dependence is one of the most critical social problems, but opioid dependence is relatively rare. Pentazocine was called the non-addictive opioid at the time of development and release and there are few reports of its dependence. We experienced a medical worker with pentazocine dependence. He started to use pentazocine to reduce serious migraine and felled into dependence by changing the purpose to relaxation of stammering fear and strain towards other people. He was successfully treated by cognitive therapy.

Topics: Adult; Analgesics, Opioid; Anti-Anxiety Agents; Cognitive Behavioral Therapy; Diazepam; Fluvoxamine; Humans; Male; Opioid-Related Disorders; Pentazocine; Substance Withdrawal Syndrome; Tranquilizing Agents; Treatment Outcome

Topics: Adult; Bipolar Disorder; Depressive Disorder; Female; Fluvoxamine; Humans; Methamphetamine; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

A microdialysis study was undertaken to determine the effect of acute and sub-chronic administration of the selective serotonin reuptake inhibitor, fluvoxamine, and the acute effect of the selective serotonin reuptake inhibitor sertraline, on the naloxone precipitated opioid withdrawal induced increase in hippocampal noradrenaline levels. This study also determined the effect of fluvoxamine and sertraline on opioid withdrawal-induced physical behaviours. Naloxone (1 mg kg(-1); i.p.) increased noradrenaline levels in the hippocampus of morphine dependent rats 20 min after administration, with peak levels of 267+/-13% of baseline, occurring 40 min after administration of naloxone. Opioid withdrawal-induced physical behaviours were evident in morphine dependent rats 5 min after a naloxone injection (1 mg kg(-1); i.p.). Acute fluvoxamine or sertraline (10 mg kg(-1); i.p.) given 40 min before naloxone (1 mg kg(-1); i.p.) did not modify the increased hippocampal noradrenaline levels (242+/-15 and 242+/-19%, respectively), observed in morphine dependent rats following an naloxone injection. Acute fluvoxamine and sertraline (10 mg kg(-1); i.p.) reduced the severity of the naloxone precipitated opioid withdrawal syndrome. Sub-chronic treatment with fluvoxamine (10 mg kg(-1); i.p.) prevented the naloxone precipitated increase in hippocampal noradrenaline levels in morphine dependent rats. Furthermore, sub-chronic fluvoxamine produced a significantly reduced baseline level of noradrenaline in these rats which was 52.5+/-8% of baseline 40 min after naloxone.

Topics: Analgesics, Opioid; Animals; Cerebral Cortex; Drug Administration Schedule; Drug Combinations; Fluvoxamine; Injections, Intraperitoneal; Male; Microdialysis; Morphine; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Sertraline; Substance Withdrawal Syndrome

The safety profile of the selective serotonin reuptake inhibitor, fluvoxamine, has been assessed in clinical and post-marketing studies. Post-marketing surveillance provides the opportunity to assess a drug's safety in every day clinical conditions in a much greater patient population than in clinical trials and therefore serves as a useful tool to detect signals for adverse effects with an incidence of less than 1 : 10,000. The safety profile of fluvoxamine was evaluated based on data from 17 years of global post-marketing surveillance in an estimated 28 million patients exposed to fluvoxamine. A total of 6,658 adverse drug reaction reports received from world-wide sources were reviewed and analysed. Post-marketing surveillance data confirmed the favourable safety profile already observed in clinical and post-marketing studies. A remarkably low level of suicidality, switch to mania, and sexual dysfunction was found. Serotonin syndrome appeared to be a very rare complication of fluvoxamine treatment. No signals for drug interactions unknown so far were identified. Withdrawal symptoms were observed in everyday clinical conditions, which were generally mild and resolved spontaneously. However, no cases suggestive for drug dependence have been reported. In conclusion, the data presented underlined that fluvoxamine offers a safe and well-tolerated option in the treatment of depression and obsessive-compulsive disorder.

Topics: Antidepressive Agents, Second-Generation; Bipolar Disorder; Cardiovascular Diseases; Death; Drug Interactions; Fluvoxamine; Humans; Product Surveillance, Postmarketing; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Serotonin Syndrome; Sexual Dysfunctions, Psychological; Substance Withdrawal Syndrome; Suicide

There are reports that abrupt withdrawal of various selective serotonin re-uptake inhibitors, such as fluvoxamine, can elicit in patients various withdrawal symptoms. Fluvoxamine has been widely used in Japan for approximately 1 year. However, there have been no case reports of withdrawal symptoms following abrupt fluvoxamine discontinuation in Japan. The author reports a case where the abrupt discontinuation of fluvoxamine produced restlessness in a depressed patient. The restlessness disappeared soon after the reinstatement of treatment with fluvoxamine. This case report suggests that clinicians should carefully scrutinize a patient's compliance to fluvoxamine as the withdrawal symptoms observed following abrupt discontinuation might be regarded as a relapse of depression or side-effects of the medicine.

Topics: Adult; Depressive Disorder; Fluvoxamine; Humans; Male; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

Topics: Citalopram; Drug Administration Schedule; Fever; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Substance Withdrawal Syndrome

Methadone has been effectively used in the treatment of opiate dependence. Adequate dose and blood level have correlated with success in treatment. A number of factors including the regular use of alcohol, medications, and urinary pH can influence blood level and thereby effectiveness. Fluvoxamine has been shown to increase methadone blood levels.. Single case report.. A patient unable to maintain an effective methadone blood level despite a dose of 200 mg per day was administered fluvoxamine with subsequent increase in her methadone blood level and reduction of opiate withdrawal symptoms.. In patients unable to maintain an effective methadone blood level throughout the dosing interval, fluvoxamine can help increase the methadone blood level and alleviate opiate withdrawal symptoms.

Topics: Adult; Drug Interactions; Female; Fluvoxamine; Humans; Methadone; Narcotics; Opioid-Related Disorders; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

This study used fluorine-19 magnetic resonance spectroscopy (19F MRS) to characterize the elimination of fluvoxamine from the human brain after abrupt drug discontinuation. The elimination half-lives of fluvoxamine in brain and plasma were determined to assess their interdependence and the relationship of brain half-life to the clinical practice of drug holidays and reports of acute withdrawal symptoms.. Six subjects completing clinical treatment with fluvoxamine were enrolled in the study. Spectroscopic quantification of whole brain fluvoxamine concentrations and chromatographic determination of plasma fluvoxamine levels were performed serially for up to 10 days after drug withdrawal. Psychiatric evaluation to assess withdrawal symptoms was also done at each scanning session.. Elimination of fluvoxamine in the brain and plasma was optimally described by first-order kinetics; the mean elimination half-lives were 58 hours and 26 hours, respectively. The mean ratio of fluvoxamine brain elimination half-life to plasma half-life was 2.4. Three of the six subjects experienced mild to moderate withdrawal symptoms between the third and fifth days of the study, which corresponded to between one and two brain half-lives of fluvoxamine.. The brain elimination half-life for fluorinated psychotropic compounds can be measured noninvasively by 19F MRS. The elimination half-life of fluvoxamine was found to be substantially longer for the brain than for plasma. The time course of withdrawal symptom onset and the rationale for drug holidays with fluvoxamine appear to be well explained by the brain elimination half-life.

Topics: Brain; Brain Chemistry; Dose-Response Relationship, Drug; Female; Fluorine; Fluvoxamine; Half-Life; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Substance Withdrawal Syndrome

Topics: Adult; Female; Fluvoxamine; Humans; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

Topics: Adult; Antidepressive Agents; Citalopram; Female; Fluvoxamine; Humans; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Substance Withdrawal Syndrome

We studied reported withdrawal symptoms in a retrospective chart review of 352 patients treated in an outpatient clinic with the nonselective serotonin reuptake inhibitor clomipramine or with one of the selective serotonin reuptake inhibitors (SSRIs), fluoxetine, fluvoxamine, paroxetine, or sertraline. In 171 patients who were supervised during medication tapering and discontinuation, the most common symptoms were dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood. When patients with at least one qualitatively new symptom were defined as cases, these symptoms occurred significantly more frequently in patients who had been treated either with one of the shorter half-life SSRIs, fluvoxamine or paroxetine (17.2%), or with clomipramine (30.8%), than in patients taking one of the SSRIs with longer half-life metabolites, sertraline or fluoxetine (1.5%). The rate was not significantly different between the different shorter half-life treatments. Cases treated with fluvoxamine or paroxetine had received a significantly longer period of treatment (median 28 weeks) than noncases (16 weeks), but there were no significant associations with age or with diagnostic grouping. There was a trend toward an association with male sex. The majority of cases occurred despite slowly tapered withdrawal. Symptoms persisted for up to 21 days (mean = 11.8 days) after onset. These symptoms were relieved within 24 hours by restarting the medication, but were not relieved by benzodiazepines or by moclobemide. A role has been suggested for serotonin in coordinating sensory and autonomic function with motor activity. We suggest that this may lead to useful hypotheses about the pathophysiology of withdrawal symptoms from serotonin reuptake inhibitors.

Topics: 1-Naphthylamine; Adolescent; Adult; Age Factors; Clomipramine; Dizziness; Female; Fluvoxamine; Humans; Male; Middle Aged; Paresthesia; Paroxetine; Retrospective Studies; Selective Serotonin Reuptake Inhibitors; Sertraline; Sex Factors; Substance Withdrawal Syndrome

1. We have addressed the question of whether there is a 'serotonin withdrawal syndrome' by analysis of spontaneous reports of suspected adverse drug reactions (ADRs) associated with four SSRIs. A comparison of the post-marketing safety profiles of the four SSRIs has also been made. 2. The UK database of ADRs was examined for reactions associated with fluoxetine, fluvoxamine, paroxetine and sertraline. The safety profiles of the four SSRIs were similar. However, withdrawal reactions with paroxetine constitute a greater proportion of reports (5.1%) than with the other SSRIs (0.06-0.9%). They have been reported more often with paroxetine (0.3 reports per thousand prescriptions) than with sertraline and fluvoxamine (0.03), and least often with fluoxetine (0.002). 3. Descriptions of withdrawal reactions received and further details of 217 reports of withdrawal reaction with paroxetine obtained by mailing a questionnaire to the reporting doctor were examined. Withdrawal symptoms were diverse but most commonly comprised dizziness, paraesthesia, tremor, anxiety, nausea and palpitation. They usually occurred after 2 days and lasted for an average of 10 days. There was no evidence of a physical drug dependency syndrome. 4. Symptoms different from the previous depressive illness occur after discontinuing an SSRI, and are reported most often with paroxetine. Paroxetine is the most pharmacologically specific of the SSRIs, but it is not clear whether the reactions constitute a 'serotonin withdrawal syndrome'.

Topics: 1-Naphthylamine; Adult; Female; Fluoxetine; Fluvoxamine; Humans; Male; Paroxetine; Product Surveillance, Postmarketing; Selective Serotonin Reuptake Inhibitors; Sertraline; Substance Withdrawal Syndrome

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

Topics: 1-Naphthylamine; Fluvoxamine; Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Substance Withdrawal Syndrome

We evaluated patients abruptly withdrawn from fluvoxamine, a serotonin selective reuptake inhibitor, for evidence of a discontinuation syndrome.. In an open-label study, 14 subjects were abruptly withdrawn from fluvoxamine after treatment lasting 8 months (7 months for 1 patient). Psychological, somatic, and perceptual symptoms were assessed at Day 5, Day 10, and Day 14 postdiscontinuation. Anxiety and depression were assessed using clinician and self-rated scales.. Twelve (86%) of 14 subjects developed new symptoms. The most frequent symptoms reported were dizziness/incoordination, headaches, nausea, and irritability. Symptoms peaked on Day 5 postdiscontinuation. Only 1 subject had a recurrence of panic, but another developed anxiety and depression; both were remedicated.. Abrupt fluvoxamine discontinuation is associated with a characteristic syndrome in many patients.

Topics: Adult; Anxiety Disorders; Depressive Disorder; Dizziness; Female; Fluvoxamine; Follow-Up Studies; Humans; Male; Panic Disorder; Psychiatric Status Rating Scales; Recurrence; Severity of Illness Index; Substance Withdrawal Syndrome; Syndrome

The authors describe three patients whose panic disorder began during recreational use of MDMA (Ecstasy) and was subsequently complicated by agoraphobic avoidance that continued autonomously after cessation of the drug. Their panic disorder responded well to serotoninergic antidepressant drugs. Theoretical and practical implications are discussed.

Topics: 3,4-Methylenedioxyamphetamine; Adult; Agoraphobia; Alcohol Drinking; Amitriptyline; Arousal; Fluvoxamine; Humans; Male; N-Methyl-3,4-methylenedioxyamphetamine; Panic Disorder; Recurrence; Substance Withdrawal Syndrome; Tranylcypromine

Topics: Adult; Bipolar Disorder; Female; Fluvoxamine; Humans; Obsessive-Compulsive Disorder; Pregnancy; Pregnancy Complications; Substance Withdrawal Syndrome

Fluvoxamine 25-200 mg daily and clomipramine 25-200 mg daily were given for separate three week periods to 18 subjects with narcolepsy and cataplexy. Both drugs improved cataplexy but not narcolepsy. Fluvoxamine was less active than clomipramine, but both drugs abolished cataplexy in individual subjects. Gastrointestinal side effects prevented treatment with fluvoxamine in five subjects. All patients completed the clomipramine phase of the trial, but two men complained of delayed ejaculation. Fluvoxamine is a more potent inhibitor of 5-hydroxytryptamine (5-HT) reuptake in some systems, but not in others. It is therefore uncertain whether the greater anticataplectic effect of clomipramine is due to a greater inhibition of 5-HT reuptake or to other mechanisms.

Topics: Adult; Aged; Cataplexy; Clomipramine; Dose-Response Relationship, Drug; Female; Fluvoxamine; Humans; Male; Middle Aged; Narcolepsy; Oximes; Serotonin Antagonists; Substance Withdrawal Syndrome