Biomedical subjects
N Cutler
Publications and source records attributed to N Cutler.
Distinct mechanism for antidepressant activity by blockade of central substance P receptors.
The localization of substance P in brain regions that coordinate stress responses and receive convergent monoaminergic innervation suggested that substance P antagonists might have psychotherapeutic properties. Like clinically used antidepressant and anxiolytic drugs, substance P antagonists suppressed isolation-induced vocalizations in guinea pigs. In a placebo-controlled trial in patients with moderate to severe major depression, robust antidepressant effects of the substance P antagonist MK-869 were consistently observed. In preclinical studies, substance P antagonists did not interact with monoamine systems in the manner seen with established antidepressant drugs. These findings suggest that substance P may play an important role in psychiatric disorders.
Rizatriptan (MAXALT) for the acute treatment of migraine and migraine recurrence. A placebo-controlled, outpatient study. Rizatriptan 022 Study Group.
Rizatriptan is a novel 5-HT1B/1D agonist which is rapidly absorbed after oral administration. The efficacy and tolerability of oral rizatriptan (5 mg and 10 mg) were examined in this multicenter, double-blind, outpatient study of 1473 migraineurs which featured randomized, placebo-controlled treatment of migraine recurrences. On experiencing moderate or severe migraine headaches, patients rated headache severity prior to dosing and at 30-minute intervals for 2 hours after dosing. Onset of effect was seen as early as 30 minutes after dosing with rizatriptan 10 mg. At 2 hours postdose, the percentage of patients with pain relief was significantly higher after rizatriptan 5 mg (62%) or 10 mg (71%) compared with placebo (35%). Complete relief was also significantly higher after rizatriptan 5 mg (33%) and 10 mg (42%) compared with placebo (10%). In patients experiencing headache recurrence after initial benefit, further relief was obtained in 71% with rizatriptan 5 mg (placebo 54%) and in 82% with rizatriptan 10 mg (placebo 44%). Complete relief of recurrent headache was obtained in 36% with rizatriptan 5 mg, 49% with rizatriptan 10 mg, and 15% with placebo (P < 0.05). The most common drug-related adverse experiences were dizziness, somnolence, asthenia/fatigue, and nausea (the incidences of which were low and dose related). There was no increase in the incidence of adverse experiences after use of up to three doses of rizatriptan within 24 hours. We conclude that both doses of rizatriptan are effective and well tolerated in the acute treatment of migraine and migraine recurrence, with the 10-mg dose preferred as it is more effective with a faster onset of action.
Placebo-controlled comparison of the clinical effects of rapid discontinuation of ipsapirone and lorazepam after 8 weeks of treatment for generalized anxiety disorder.
One hundred and sixty patients (mean age 39.8 years; 67% female) diagnosed with generalized anxiety disorder (GAD) who had completed a prospective, 8 week, double-blind comparison of lorazepam (mean daily dose 4.2 mg) and ipsapirone (mean daily dose 19.5 mg) were rapidly tapered by a substitution of half-strength medication for 3 days, then substitution of matched placebo for an additional 11 days. Patients treated with ipsapirone showed no rebound anxiety on discontinuation, nor any other significant increase in withdrawal symptomatology compared to patients who had been prospectively treated with placebo. In contrast, patients treated with lorazepam showed significant emergent anxiety and/or withdrawal-related symptomatology by almost all clinical measures employed. Overall, 25% of patients treated with lorazepam showed rebound anxiety, and 40% of them utilized reserve medication because they found drug discontinuation to be intolerable. The clinical implications for discontinuation of benzodiazepines after short-term therapy are discussed.
Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia.
The effects of equi-efficacious doses of the cholesterol-lowering drugs simvastatin (20 mg day-1) and pravastatin (40 mg day-1) on tests of cognitive function were investigated in a double-blind, placebo-controlled, 2-period (4 weeks per period), incomplete block, crossover study of 36 patients (24 per treatment) with hypercholesterolaemia. After 4 weeks neither of the active treatments differed significantly from placebo on any cognitive measure.
Oral sumatriptan for the long-term treatment of migraine: clinical findings.
This double-blind, placebo-controlled, crossover study of the acute treatment of migraine investigated the efficacy and tolerability of oral sumatriptan 100 mg (Imitrex) administered for up to nine attacks compared with placebo administered for up to three attacks. Patients were randomized to receive oral sumatriptan 100 mg or placebo on an outpatient basis in a 3:1 ratio for three four-attack blocks. Headache relief 4 hours postdose was observed in 59 to 65% of patients after sumatriptan treatment compared with 18 to 23% of patients after placebo treatment across three four-attack blocks (p < 0.005). For each block, oral sumatriptan 100 mg was also significantly more effective than placebo at relieving clinical disability and nausea and vomiting. Efficacy on all these measures was consistently maintained with repeated administration. Oral sumatriptan 100 mg was well tolerated, and repeated administration did not alter the pattern or severity of adverse events. These data demonstrate that the efficacy and tolerability of oral sumatriptan 100 mg was consistently maintained with repeated administration for up to nine separate migraine attacks.
Oral sumatriptan for the acute treatment of migraine: evaluation of three dosage strengths.
This randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy and tolerability of oral sumatriptan (Imitrex tablets) in 259 migraineurs. In the clinic, patients received oral sumatriptan 25 mg, 50 mg, or 100 mg, or placebo for the treatment of a migraine attack. The results indicate that by 2 hours post-dose, 50 to 56% of patients treated with any of the three doses, compared with 26% of patients treated with placebo, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). By 4 hours postdose, 68 to 71% of sumatriptan-treated patients, compared with 38% of placebo-treated patients, achieved relief of headache (p < 0.05 for each sumatriptan group vs placebo). Oral sumatriptan was similarly effective at relieving nausea and photophobia and at reducing clinical disability. The pattern and incidence of adverse events did not differ between treatment groups. All doses--25 mg, 50 mg, and 100 mg--of sumatriptan were effective and generally well tolerated. Dosing should be individualized according to the needs of the patient.
Relationship between duration of illness and plasma concentrations of antipsychotics in psychotic patients.
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Subjective neuroleptic response and treatment outcome under open and double-blind conditions--a preliminary report.
1. A patient's early subjective response to a neuroleptic was recorded in 17 schizophrenic patients following a fixed dose of neuroleptic under both open and double-blind placebo-controlled conditions. 2. High correlations were found between a patient's subjective response at 2.5, 24 and 48 hours after the initial dose, suggesting that the timing of the initial subjective response rating is not critical. 3. The relationship between the psychiatric improvement and subjective response was not significant under double-blind conditions (r = 0.004), while the relationship under the open condition showed a trend towards significance comparable to earlier reports (r = 0.32). 4. The findings question the usefulness of applying early subjective response to a neuroleptic to predict clinical improvement.
Computer-assisted categorization of brain computerized tomography pixels into cerebrospinal fluid, white matter, and gray matter.
A computer-assisted method was employed to estimate the amounts of cerebrospinal fluid (CSF), white matter, and gray matter in individual computerized tomography (CT) scans of brains. By means of an image processing procedure (DMORPH), the means +/- SD CT numbers of "pure" CSF, white matter, and gray matter were determined in each scan and stored. A CATSEG program used these means to define ranges for CT numbers for each of the three tissues on each scan, and to assign each pixel in a scan to one of the three categories. Summing over seven serial scans provided volumetric estimates of CSF, white matter, and gray matter in a brain segment. For 10 subjects aged 21 to 43 years, CSF volume equaled 1.4 to 4.7% of the total segment volume, white matter equaled 37.5 to 48.2%, and gray matter equaled 50.2 to 58.9%. Image processing hardware and software which allow standardized sampling from CT images for the evaluation of surface areas and CT numbers are described. These procedures, as applied to CT scans of the human brain, can be used to estimate the volumes of CSF, white matter, and gray matter in a selected intracranial segment.
Tricyclic antidepressants.
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Tricyclic antidepressants.
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Retrospective diagnosis of hypomania following successful treatment of episodic violence with lithium: a case report.
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