Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial.
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BACKGROUND: Patients with atypical depression are more likely to respond to monoamine oxidase inhibitors than to tricyclic antidepressants. They are frequently offered psychotherapy in the absence of controlled tests. There are no prospective, randomized, controlled trials, to our knowledge, of psychotherapy for atypical depression or of cognitive therapy compared with a monoamine oxidase inhibitor. Since there is only 1 placebo-controlled trial of cognitive therapy, this trial fills a gap in the literature on psychotherapy for depression. METHODS: Outpatients with DSM-III-R major depressive disorder and atypical features (N = 108) were treated in a 10-week, double-blind, randomized, controlled trial comparing acute-phase cognitive therapy or clinical management plus either phenelzine sulfate or placebo. Atypical features were defined as reactive mood plus at least 2 additional symptoms: hypersomnia, hyperphagia, leaden paralysis, or lifetime sensitivity to rejection. RESULTS: With the use of an intention-to-treat strategy, the response rates (21-item Hamilton Rating Scale for Depression score, < or =9) were significantly greater after cognitive therapy (58%) and phenelzine (58%) than after pill placebo (28%). Phenelzine and cognitive therapy also reduced symptoms significantly more than placebo according to contrasts after a repeated-measures analysis of covariance and random regression with the use of the blind evaluator's final Hamilton Rating Scale for Depression score. The scores between cognitive therapy and phenelzine did not differ significantly. Supplemental analyses of other symptom severity measures confirm the finding. CONCLUSIONS: Cognitive therapy may offer an effective alternative to standard acute-phase treatment with a monoamine oxidase inhibitor for outpatients with major depressive disorder and atypical features. (+info)
Effects of chronic antidepressant treatments on serotonin transporter function, density, and mRNA level.
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To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with the selective serotonin reuptake inhibitors (SSRIs) paroxetine or sertraline, the selective norepinephrine reuptake inhibitor desipramine (DMI), or the monoamine oxidase inhibitor phenelzine. High-speed in vivo electrochemical recordings were used to assess the ability of the SSRI fluvoxamine to modulate the clearance of locally applied serotonin in the CA3 region of hippocampus in drug- or vehicle-treated rats. Fluvoxamine decreased the clearance of serotonin in rats treated with vehicle, DMI, or phenelzine but had no effect on the clearance of serotonin in SSRI-treated rats. SERT density in the CA3 region of the hippocampus of the same rats, assessed by quantitative autoradiography with tritiated cyanoimipramine ([(3)H]CN-IMI), was decreased by 80-90% in SSRI-treated rats but not in those treated with phenelzine or DMI. The serotonin content of the hippocampus was unaffected by paroxetine or sertraline treatment, ruling out neurotoxicity as a possible explanation for the SSRI-induced decrease in SERT binding and alteration in 5-HT clearance. Levels of mRNA for the SERT in the raphe nucleus were also unaltered by chronic paroxetine treatment. Based on these results, it appears that the SERT is downregulated by chronic administration of SSRIs but not other types of antidepressants; furthermore, the downregulation is not caused by decreases in SERT gene expression. (+info)
Anaphylaxis and monoamine oxidase inhibitors--the use of adrenaline.
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A 67 year old woman taking a monoamine oxidase inhibitor (MAOI) presented to the accident and emergency department with an anaphylactic reaction to flucloxacillin. This case highlights the uncertainty regarding the use of adrenaline (epinephrine) in the context of concurrent MAOI use. A summary of the evidence is presented to clarify this. (+info)
Safe use of remifentanil in a patient treated with the monoamine oxidase inhibitor phenelzine.
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We report the safe use of remifentanil as part of the anaesthetic technique in a patient undergoing major head and neck surgery who was being treated for depressive illness with the non-specific monoamine oxidase inhibitor (MAOI) phenelzine. (+info)
Common effects of chronically administered antipanic drugs on brainstem GABA(A) receptor subunit gene expression.
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Panic disorder is an anxiety disorder that can be treated by long-term administration of tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors such as phenelzine, or the selective serotonin reuptake inhibitor (SSRI) antidepressants. Clinical data also indicate that some benzodiazepines, such as alprazolam, are effective antipanic agents, and that their therapeutic onset is faster than that of antidepressants. Benzodiazepines are well known for their action at GABA(A) receptors, and preclinical data indicate that imipramine and phenelzine also interfere with the GABAergic system. In addition some clinical data lend support to decreased benzodiazepine-sensitive receptor function in panic disorder patients. Using imipramine, phenelzine and alprazolam, we investigated, in rats, the possibility that the therapeutic efficacy of antipanic agents stems from the remodeling of GABAergic transmission in the pons-medulla region. Of the 12 GABA(A) receptor subunit (alpha 1--6, beta 1--3, gamma 1--3) steady-state mRNA levels investigated, we observed an increase in the levels of the alpha 3-, beta 1- and gamma 2-subunit transcripts with all three antipanic agents tested. The effects of imipramine and phenelzine on these subunits occurred after 21 days of treatment, while alprazolam effects were observed after 3 days of administration. Histochemical data suggest that the alpha 3 beta 1 gamma 2 subunits comprise a receptor subtype in the pons-medulla region. Therefore, we conclude that these molecular events parallel the therapeutic profile of the drugs examined. We further propose that these events may correspond to a remodeling of the GABA(A) receptor population, and may be useful markers for investigation of the antipanic properties of drugs. (+info)
Effect of chronic phenelzine treatment on REM sleep: report of three patients.
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Antidepressants belonging to the class of monoamine oxidase inhibitors (MAOI) such as phenelzine have long been known to drastically suppress REM sleep. Sleep and the electroencephalogram (EEG) in sleep and waking were studied in three depressed patients at regular time intervals before, during and after 6 to 18 months of phenelzine treatment. While REM sleep was initially eliminated in all patients, short REM sleep episodes reappeared after three to six months of medication. Total sleep time and EEG slow-wave activity (SWA, spectral power within 0.75-4.5 Hz) in nonREM sleep (stages 1-4) were not changed. In contrast, EEG theta frequency activity (TFA, power within 4.75-8.0 Hz) during a 5-min wake interval recorded prior to the sleep episodes was initially enhanced, and tended to correlate negatively with the percentage of REM sleep (p =.06). This observation indicates that compensatory REM sleep mechanisms may occur in wakefulness during chronic MAOI treatment. (+info)
Clonidine potentiates the effects of tranylcypromine, phenelzine and two analogues in the forced swimming test in mice.
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OBJECTIVE: To compare tranylcypromine (TCP) and phenelzine (PLZ), two well-established inhibitors of monoamine oxidase (MAO), and 2 of their analogues, 4-fluorotranylcypromine (FTCP) and N2-acetylphenelzine (AcPLZ) respectively, with regard to effects in the forced swimming test, a behavioural test used to screen for potential antidepressant drugs. METHODS: Mice were dropped individually into glass cylinders containing water. The duration of their immobility was scored during the last 4 minutes of the test. RESULTS: Except for TCP at high doses, none of the drugs demonstrated activity when administered alone. All 4 drugs were active when given in combination with clonidine, an effect thought to be the result of mixed action at 5-HT1A and 5-HT2 receptors and the noradrenergic system. 5-HT18 receptors do not seem to be implicated, as lithium did not potentiate the effect of any of the drugs. Quinine activation of AcPLZ suggests that this analogue acts on 5-HT3 receptors. CONCLUSIONS: FTCP and AcPLZ demonstrated anti-immobility activity in the forced swimming test when used in association clonidine. These findings confirm previous neurochemical findings suggesting that these drugs have antidepressant properties. (+info)
Different effects of phenelzine treatment on EEG topography in waking and sleep in depressed patients.
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A novel approach to investigate the relationship between depression and changes in sleep-wake regulatory mechanisms used the monoamine oxidase inhibitor (MAOI) phenelzine that is known to suppress rapid-eye-movement (REM) sleep. Sleep architecture and EEG topography during wakefulness and sleep were studied in eight depressed patients before and after five weeks of treatment with phenelzine (30-90 mg/day), which induced a significant alleviation of depressive symptoms. Theta power (4.75-7.5 Hz) during a 5-min wake EEG prior to sleep increased two-fold during administration of phenelzine. REM sleep was almost completely eliminated. This latter effect was compensated by increased duration of stage 2, whereas total sleep time was not shortened. In non-REM sleep (stages 2, 3, and 4), treatment slightly reduced EEG power between 2.0-6.25 Hz and 8.5-13.75 Hz; power in the 16.75-25.0 Hz band increased. Activity in the delta band (2.0-3.25 Hz) tended to be reduced in the fronto-central derivation, but not in centro-parietal and parieto-occipital derivations. However, the Treatment X Derivation interaction was not significant. These data indicate that in contrast to wakefulness the effects of phenelzine treatment on the EEG in non-REM sleep were small. Rank correlation analyses revealed no association between the antidepressant treatment response and the changes in sleep and EEG power spectra during administration of phenelzine. (+info)