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1.
Arch Gen Psychiatry ; 58(7): 681-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11448376

ABSTRACT

BACKGROUND: There is debate about combining benzodiazepines with selective serotonin reuptake inhibitors in the acute treatment of panic disorder. Although this medication combination is widely used in clinical practice, there is no well-tested, optimal method of coadministering these medications for the treatment of panic disorder. The purpose of this study was to test the efficacy of early coadministration of clonazepam with sertraline in the treatment of panic disorder. METHODS: Fifty patients with panic disorder were randomized into a double-blind clinical trial. Patients received open-label sertraline for 12 weeks (target dose, 100 mg/d), and in addition were randomized to groups receiving either 0.5 mg of active clonazepam 3 times daily or placebo clonazepam for the first 4 weeks of the trial. The clonazepam dose was then tapered during 3 weeks and discontinued. RESULTS: Thirty-four (68%) of 50 patients completed the trial. Drop-out rates were similar in the sertraline/placebo vs the sertraline/clonazepam group (38% vs 25%) (P =.5). An intent-to-treat analysis (on last observation carried forward data) revealed a much greater proportion of responders in the sertraline/clonazepam compared with the sertraline/placebo group at the end of week 1 of the trial (41% vs 4%) (P =.003). There was also a significant between-group difference at the end of week 3 with 14 (63%) of 22 of the sertraline/clonazepam group responding to treatment vs 8 (32%) of 25 of the sertraline/placebo group (P =.05). This difference was not observed at other times during the trial. CONCLUSION: These data indicate that rapid stabilization of panic symptoms can be safely achieved with a sertraline/clonazepam combination, supporting the clinical utility of this type of regimen for facilitating early improvement of panic symptoms relative to sertraline alone.


Subject(s)
Clonazepam/therapeutic use , Panic Disorder/drug therapy , Selective Serotonin Reuptake Inhibitors/therapeutic use , Sertraline/therapeutic use , Adult , Anticonvulsants , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Male , Panic Disorder/diagnosis , Panic Disorder/psychology , Placebos , Psychiatric Status Rating Scales/statistics & numerical data , Treatment Outcome
2.
Arch Gen Psychiatry ; 58(6): 556-61, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11386984

ABSTRACT

BACKGROUND: There is preclinical evidence and indirect clinical evidence implicating gamma-aminobutyric acid (GABA) in the pathophysiology and treatment of human panic disorder. Specifically, deficits in GABA neuronal function have been associated with anxiogenesis, whereas enhancement of GABA function tends to be anxiolytic. Although reported peripheral GABA levels (eg, in cerebrospinal fluid and plasma) have been within reference limits in panic disorder, thus far there has been no direct assessment of brain GABA levels in this disorder. The purpose of the present work was to determine whether cortical GABA levels are abnormally low in patients with panic disorder. METHODS: Total occipital cortical GABA levels (GABA plus homocarnosine) were assessed in 14 unmedicated patients with panic disorder who did not have major depression and 14 retrospectively age- and sex-matched control subjects using spatially localized (1)H-magnetic resonance spectroscopy. All patients met DSM-IV criteria for a principal current diagnosis of panic disorder with or without agoraphobia. RESULTS: Patients with panic disorder had a 22% reduction in total occipital cortex GABA concentration (GABA plus homocarnosine) compared with controls. This finding was present in 12 of 14 patient-control pairs and was not solely accounted for by medication history. There were no significant correlations between occipital cortex GABA levels and measures of illness or state anxiety. CONCLUSIONS: Panic disorder is associated with reductions in total occipital cortex GABA levels. This abnormality might contribute to the pathophysiology of panic disorder.


Subject(s)
Magnetic Resonance Spectroscopy/statistics & numerical data , Occipital Lobe/chemistry , Panic Disorder/diagnosis , gamma-Aminobutyric Acid/analysis , Adult , Agoraphobia/diagnosis , Agoraphobia/metabolism , Ambulatory Care , Carnosine/analogs & derivatives , Carnosine/analysis , Carnosine/metabolism , Female , Humans , Male , Occipital Lobe/metabolism , Panic Disorder/metabolism , Panic Disorder/physiopathology , gamma-Aminobutyric Acid/metabolism , gamma-Aminobutyric Acid/physiology
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