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Biomedical subjects

L H Price

Publications and source records attributed to L H Price.

At least 145 records · Page 8Linked to original sources
PubMed1990

After lithium augmentation: a retrospective follow-up of patients with antidepressant-refractory depression.

There have been no systematic follow-up studies of depressed patients with documented refractoriness to antidepressants treated with lithium augmentation. To assess their longitudinal course, 66 (88%) of an original cohort of 75 such patients were followed in a retrospective, naturalistic design for 29.0 +/- SD 15.3 months. At follow-up, 29% had poor, 23% fair, and 48% good outcomes. An acute marked positive response to lithium augmentation predicted a good subsequent course. Acute partial and non-responders had a less benign outcome despite subsequent treatments. These findings indicate that outcomes of patients with documented refractory depression are heterogeneous. There is a suggestion that an acute marked response to lithium augmentation is sustained regardless of the duration of taking lithium, but this must be regarded as speculative.

Adult↗
PubMed1990

Clinical studies of 5-HT function using i.v. L-tryptophan.

1. Preclinical studies reveal that long-term treatment with antidepressant drugs induces significant changes in serotonergic (5-HT) receptor sensitivity. Similarly, clinical studies suggest that brain 5-HT function is abnormal in depression. Of the available methodologies for conducting such clinical studies, the pharmacological challenge strategy has proven particularly useful. 2. I.v. L-TRP has emerged as the most frequently used challenge agent in diagnostic and neuropsychopharmacological studies of 5-HT function. I.v. L-TRP increases serum prolactin (PRL) in humans, probably via 5-HT mechanisms. Under carefully standardized conditions, this PRL response to L-TRP appears to be a reasonably sensitive and valid measure of net 5-HT function. 3. The PRL response to L-TRP is blunted in depressed patients compared with healthy controls. Blunting has not been observed in panic disorder, obsessive compulsive disorder, or schizophrenia, although preliminary findings suggest it may occur in bulimia. 4. The PRL response to L-TRP is enhanced by certain classes of thymoleptic drugs (TCAs, MAOIs, 5-HT reuptake inhibitors, lithium) in a differentially time-dependent fashion. So-called "atypical" antidepressants (trazodone, mianserin) and benzodiazepines have no effect. Such findings are generally consistent with preclinical electrophysiological findings. 5. These clinical studies of the PRL response to L-TRP, in conjunction with emerging evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants, suggest that antidepressant drug action may be more accurately conceptualized as 5-HT dependent rather than 5-HT enhancing. The availability of more selective 5-HT-active drugs promises to further clarify 5-HT mechanisms of neuropsychiatric disease and drug action at the clinical level.

Animals↗
PubMed1990

Opioid antagonist challenges in buprenorphine maintained patients.

Following one month of sublingual buprenorphine treatment, 15 patients at either 2 mg (n = 7) or 3 mg (n = 8) were hospitalized and the buprenorphine was abruptly stopped by placebo substitution. On the morning following their last dose of buprenorphine, 10 patients were given 1 mg oral naltrexone and 5 were given 0.5 mg/kg intravenous naloxone in a double blind placebo controlled challenge. The naltrexone challenges produced no increase in opioid withdrawal symptoms, plasma MHPG levels, or blood pressure compared to placebo, while naloxone produced significant symptoms and blood pressure increases compared to placebo challenges.

Administration, Sublingual↗
PubMed1990

Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder.

Nine of 17 patients with obsessive-compulsive disorder responded when neuroleptic was added to fluvoxamine with or without lithium. Comorbid occurrence of tic spectrum disorders or of schizotypal personality disorder was associated with response. Abnormalities in brain dopamine and serotonin may be implicated in such patients.

Adult↗
PubMed1990

Fluvoxamine/pimozide treatment of concurrent Tourette's and obsessive-compulsive disorder.

A 25-year-old man with a history of Tourette's syndrome presented for treatment of OCD symptoms. Fluvoxamine worsened tics, led to coprolalia, and did not help the OCD. The addition of pimozide dramatically reduced both OCD and Tourette's symptoms. Double-blind sequential discontinuation of fluvoxamine and pimozide confirmed that pimozide alone reduced only tics and the combination of fluvoxamine and pimozide was required for the improvement in OCD. Tics may reflect a subtype of OCD. Some OCD patients unresponsive to a 5-HT reuptake inhibitor alone may benefit from the addition of a dopamine antagonist.

Adult↗
PubMed1990

Clinical data on the role of serotonin in the mechanism(s) of action of antidepressant drugs.

In view of evidence that brain serotonin (5-HT) function is abnormal in depression, the ability to alter 5-HT function has been studied as a mechanism of antidepressant drug action. In preclinical studies, antidepressants had significant effects on 5-HT receptor sensitivity. In the clinical setting, the pharmacologic challenge paradigm has generated interest as a means of studying 5-HT function. Most frequently used in these studies has been intravenous L-tryptophan (L-TRP), which increases serum prolactin (PRL). The authors review the neuroendocrine effects of intravenous L-TRP in depression and other conditions, as well as the effects of thymoleptic drugs on the PRL response to L-TRP. Findings are discussed in light of recent evidence that experimentally reduced plasma TRP can reverse the therapeutic effects of some antidepressants.

Antidepressive Agents↗
PubMed1990

Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder?

It seems unlikely that a solitary disturbance in serotonin function can fully account for the pathophysiology of obsessive compulsive disorder. The authors propose that some forms of obsessive compulsive disorder, e.g., obsessive compulsive disorder with a history of Tourette's syndrome, may involve a relative or absolute derangement in both brain serotoninergic and dopaminergic systems. A role for dopamine in the pathophysiology of obsessive compulsive disorder is supported by a review of the preclinical and clinical evidence. Additional studies are needed to more directly evaluate dopamine function in patients with obsessive compulsive disorder.

Dopamine↗
PubMed1990

Fenfluramine augmentation in tricyclic-refractory depression.

The clinical efficacy of lithium augmentation in refractory depression is hypothesized to depend on the ability of lithium to enhance presynaptic 5-hydroxytryptamine (5-HT) function. Since fenfluramine promotes release and inhibits reuptake of presynaptic 5-HT, we assessed its efficacy in augmenting ongoing tricyclic antidepressant treatment of refractory depression. Fifteen patients with DSM-III major depression failed to respond to treatment with desipramine 2.5 mg/kg/day or more (plasma levels of at least 125 ng/ml) given for at least 4 weeks. Fenfluramine 40-120 mg/day was then added to the ongoing desipramine in a placebo substitution design. There was no statistically significant evidence of either transient or sustained clinical improvement during the 2 weeks of fenfluramine augmentation. One patient appeared to respond to the treatment, but one appeared to worsen. Fenfluramine more than doubled steady-state plasma levels of desipramine. These findings suggest that lithium's efficacy as an augmenting agent depends on properties that are not shared by fenfluramine. Fenfluramine cannot be recommended in the routine management of refractory depression.

Adult↗
PubMed1989

Lithium treatment and serotoninergic function. Neuroendocrine and behavioral responses to intravenous tryptophan in affective disorder.

Evidence suggests that lithium treatment alters serotoninergic (5-HT) function in laboratory animals and humans. Since 5-HT function may be abnormal in patients with affective disorders, we studied 23 such patients by measuring responses to intravenous infusion of the 5-HT precursor tryptophan before and during short-term (less than one week) or long-term (greater than three weeks) lithium treatment. The prolactin response to tryptophan was significantly enhanced after short-term lithium treatment; long-term lithium treatment had no effect. Other studies have shown that the prolactin response to tryptophan is also enhanced after long-term tricyclic antidepressant treatment in depressed patients and after short- and long-term lithium treatment in healthy subjects. The present findings suggest that lithium treatment enhances 5-HT function, but that homeostatic responses of the 5-HT system to long-term lithium treatment may differ in patients with affective disorder and healthy subjects.

Adult↗
PubMed1989

Neuroendocrine and mood responses to intravenous L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users. Preliminary observations.

3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a selective serotonin (5-HT) neurotoxin in laboratory animals. To assess its effects on 5-HT function in humans, serum prolactin (PRL) and mood responses to intravenous L-tryptophan were measured in nine recreational users of MDMA and compared with findings from nine matched healthy controls. L-Tryptophan induced a rise in the PRL concentration in controls, but not in MDMA users. Peak change and the area under the curve of the PRL response appeared to be blunted in MDMA users, but the difference from controls did not reach statistical significance. This study provides suggestive evidence of altered 5-HT function in MDMA users, but more definitive studies clearly are needed.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Efficacy of fluvoxamine in obsessive-compulsive disorder. A double-blind comparison with placebo.

A six- to eight-week double-blind placebo-controlled trial of the potent and selective serotonin reuptake inhibitor fluvoxamine was conducted in 42 patients with primary obsessive-compulsive disorder (OCD). Approximately one half of the patients also had symptoms of major depression. Fluvoxamine was significantly better than placebo on all measures of obsessive-compulsive symptoms. Nine of 21 patients were responders ("much improved") with fluvoxamine compared with no responders with placebo, and fluvoxamine was effective in patients with OCD both with and without secondary depression. Response of OCD was not correlated with severity of baseline depression. These data lend partial support to the serotonin hypothesis of OCD. However, since a number of patients failed to respond to fluvoxamine, the role of other neurochemical systems in this disorder needs to be explored.

Adult↗
PubMed1989

Effects of desipramine and fluvoxamine treatment on the prolactin response to tryptophan. Serotonergic function and the mechanism of antidepressant action.

It has been hypothesized that enhancement of brain serotoninergic (5-HT) function is involved in the mechanism of action of some antidepressants. To test this, the prolactin response to intravenously administered tryptophan, a clinical measurement of 5-HT function, was assessed before and during antidepressant treatment. Depressed patients received the tricyclic desipramine hydrochloride (N = 24) or the 5-HT reuptake inhibitor fluvoxamine maleate (N = 30). The prolactin response was significantly enhanced after long-term treatment (4 weeks) but not as reliably increased after short-term (1-week) desipramine treatment. Fluvoxamine enhanced the prolactin response after both short- and long-term treatment. Enhancement of the prolactin response was not clearly correlated with clinical improvement. The results of this study are consistent with preclinical evidence of enhanced 5-HT function during treatment with these classes of antidepressants, but also indicate that enhanced 5-HT function is not a sufficient condition for antidepressant efficacy.

Antidepressive Agents↗
PubMed1989

The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability.

The Yale-Brown Obsessive Compulsive Scale was designed to remedy the problems of existing rating scales by providing a specific measure of the severity of symptoms of obsessive-compulsive disorder that is not influenced by the type of obsessions or compulsions present. The scale is a clinician-rated, 10-item scale, each item rated from 0 (no symptoms) to 4 (extreme symptoms) (total range, 0 to 40), with separate subtotals for severity of obsessions and compulsions. In a study involving four raters and 40 patients with obsessive-compulsive disorder at various stages of treatment, interrater reliability for the total Yale-Brown Scale score and each of the 10 individual items was excellent, with a high degree of internal consistency among all item scores demonstrated with Cronbach's alpha coefficient. Based on pretreatment assessment of 42 patients with obsessive-compulsive disorder, each item was frequently endorsed and measured across a range of severity. These findings suggest that the Yale-Brown Scale is a reliable instrument for measuring the severity of illness in patients with obsessive-compulsive disorder with a range of severity and types of obsessive-compulsive symptoms.

Adult↗
PubMed1989

The Yale-Brown Obsessive Compulsive Scale. II. Validity.

The development design and reliability of the Yale-Brown Obsessive Compulsive Scale have been described elsewhere. We focused on the validity of the Yale-Brown Scale and its sensitivity to change. Convergent and discriminant validity were examined in baseline ratings from three cohorts of patients with obsessive-compulsive disorder (N = 81). The total Yale-Brown Scale score was significantly correlated with two of three independent measures of obsessive-compulsive disorder and weakly correlated with measures of depression and of anxiety in patients with obsessive-compulsive disorder with minimal secondary depressive symptoms. Results from a previously reported placebo-controlled trial of fluvoxamine in 42 patients with obsessive-compulsive disorder showed that the Yale-Brown Scale was sensitive to drug-induced changes and that reductions in Yale-Brown Scale scores specifically reflected improvement in obsessive-compulsive disorder symptoms. Together, these studies indicate that the 10-item Yale-Brown Scale is a reliable and valid instrument for assessing obsessive-compulsive disorder symptom severity and that it is suitable as an outcome measure in drug trials of obsessive-compulsive disorder.

Adult↗
PubMed1989

Neuroendocrine and behavioral effects of dietary tryptophan restriction in healthy subjects.

The neuroendocrine and behavioral effects of gradual dietary tryptophan (TRP) depletion, utilizing two magnitudes of a 10-day TRP-restriction diet (700 mg/day and 200 mg/day), were studied in 22 healthy subjects. The prolactin response to a 7 gm L-TRP infusion was measured prior to and on day 10 of the diet. Both diets significantly reduced fasting total plasma TRP by 15 to 20%, but only the 200 mg/day TRP diet led to an enhancement of the prolactin response to intravenous L-TRP. Female subjects demonstrated a more robust increase in plasma prolactin following L-TRP infusion pre-diet and exhibited a larger decrease in plasma TRP following dietary TRP restriction compared to males. There were no significant behavioral effects of either diet. Gradual dietary TRP depletion leads to an enhancement of the prolactin response to L-TRP infusion, suggestive of postsynaptic serotonin receptor supersensitivity.

Adult↗