Lithium in the treatment of mood disorders.
Explore the source record for details and available documents.
Bipolar Disorder↗
Biomedical subjects
L H Price
Publications and source records attributed to L H Price.
Haloperidol addition in fluvoxamine-refractory obsessive-compulsive disorder. A double-blind, placebo-controlled study in patients with and without tics.
BACKGROUND: To determine the efficacy of adding haloperidol to the treatment of patients with obsessive-compulsive disorder (OCD), with or without a comorbid chronic tic disorder, who were refractory to adequate treatment with the serotonin-uptake inhibitor fluvoxamine alone. It was hypothesized that OCD patients with a concurrent chronic tic disorder would preferentially respond to this treatment. METHODS: Sixty-two patients with a primary DSM-III-R diagnosis of OCD received placebo fluvoxamine for 1 week, followed by 8 weeks of active fluvoxamine. Thirty-four of these patients were refractory to fluvoxamine and were randomized in a double-blind fashion to 4 weeks of treatment with either haloperidol (n = 17) or placebo (n = 17) added to ongoing fluvoxamine treatment. The placebo-treated group included five women and 12 men, six inpatients and 11 outpatients, and eight patients with a comorbid chronic tic disorder. The haloperidol-treated group consisted of two women and 15 men, three inpatients and 14 outpatients, and seven patients with a comorbid chronic tic disorder. All 34 patients completed the entire study. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale were the principal measures of treatment outcome. RESULTS: Haloperidol addition was significantly better than placebo in reducing the severity of obsessive-compulsive symptoms as measured by the Y-BOCS. Eleven of 17 patients responded to the haloperidol, compared with none of 17 patients given placebo. Eight of eight patients with comorbid chronic tic disorders, such as Tourette's disorder, responded to double-blind haloperidol addition to ongoing fluvoxamine treatment. Haloperidol addition was of little benefit in treating OCD patients without tics. Fluvoxamine blood levels were not related to treatment response. CONCLUSIONS: The results of this study suggest that OCD patients with a comorbid chronic tic disorder constitute a clinically meaningful subtype of OCD that might require conjoint serotonin-uptake inhibitor/neuroleptic therapy for effective symptom reduction.
Adolescent↗
Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors.
METHODS: The effects of short-term tryptophan depletion were examined in 15 patients with DSM-III-R obsessive-compulsive disorder who had demonstrated symptom reduction following treatment with serotonin reuptake inhibitors. Patients received a 24-hour, low-tryptophan (160-mg/d) diet followed the next morning by a drink of 15 amino acids. A double-blind, placebo-controlled cross-over design was used. RESULTS: The diet and the amino acid drink reduced free plasma tryptophan levels by a mean of 84% 5 hours later. Short-term tryptophan depletion did not significantly change mean ratings of obsessions and compulsions. In contrast, mean depression ratings were significantly increased with tryptophan depletion compared with the control (tryptophan-supplemented) testing. CONCLUSION: Maintenance of serotonin reuptake inhibitor-induced improvement of obsessive and compulsive symptoms, unlike remission of depressive symptoms, may not depend on ongoing short-term availability of serotonin.
Adult↗
Noradrenergic dysregulation during discontinuation of cocaine use in addicts.
BACKGROUND: The primary objective of the study was to prospectively determine possible noradrenergic dysregulation in cocaine addicts by assessing biochemical, behavioral, and cardiovascular responses to intravenous yohimbine hydrochloride during early and late discontinuation of cocaine use. METHODS: Twelve male and two female hospitalized cocaine-dependent subjects (mean +/- SD age, 30.9 +/- 7.3 years) who were not seeking primary treatment for addiction participated voluntarily for monetary remuneration. Following an initial test dose of intranasal cocaine, 2 mg/kg, cocaine addicts received single-blind, monitored cocaine insufflation, 2 mg/kg three times each day, for 3 consecutive days. One to two days (early discontinuation) and 15 to 16 days (late discontinuation) after the last dose of cocaine, subjects received double-blind, randomized intravenous infusions of yohimbine hydrochloride, 0.4 mg/kg, or placebo. Plasma 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) and plasma cortisol levels, anxiety-related symptoms on clinician- and subject-rated scales, blood pressure, and heart rate were measured throughout each test day. Ten of 14 subjects completed the entire study. RESULTS: Subjects had a significantly greater placebo-corrected MHPG response to yohimbine during early compared with late discontinuation. Subjects rated themselves significantly more nervous following yohimbine administration during early compared with late discontinuation. Seventy-one percent of subjects experienced a yohimbine-induced panic attack during early discontinuation compared with none during late discontinuation. CONCLUSIONS: The results of this study provide evidence of an underlying dysregulation in noradrenergic function and a vulnerability to panic anxiety during early discontinuation of cocaine use in addicts. Additional investigations of noradrenergic function appear warranted to further clarify derangements associated with cocaine addiction.
Administration, Intranasal↗
Elevated cerebrospinal fluid levels of oxytocin in obsessive-compulsive disorder. Comparison with Tourette's syndrome and healthy controls.
BACKGROUND: Limited neurobiological data have implicated central arginine vasopressin in the pathobiology of obsessive-compulsive disorder (OCD). Based on twin, family genetic, and pharmacological studies, some forms of OCD are etiologically related to Tourette's syndrome. The role of arginine vasopressin and related compounds such as oxytocin in Tourette's syndrome has not been previously explored. METHODS: To compare cerebrospinal fluid (CSF) levels of arginine vasopressin and oxytocin, we collected CSF at midday in a standardized fashion from a total of 83 individuals (29 patients with OCD, 23 patients with Tourette's syndrome, and 31 normal controls). We also collected family study data on each subject to determine which subjects had a family history positive for Tourette's syndrome, OCD, or related syndromes. RESULTS: In contrast to previous reports, we report similar concentrations of arginine vasopressin for all three groups but increased oxytocin levels in patients with OCD. Remarkably, this increase was observed only in a subset of patients with OCD (n = 22) independently identified as being without a personal or family history of tic disorders (P = .0003). In this subgroup of patients, the CSF oxytocin level was correlated with current severity of OCD (n = 19, r = .47, P < .05). CONCLUSIONS: A possible role for oxytocin in the neurobiology of a subtype of OCD is suggested by the elevated CSF levels of oxytocin and by the correlation between CSF oxytocin levels and OCD severity. These findings reinforce the value of family genetic data in identifying biologically homogeneous (and perhaps more etiologically homogeneous) groups of patients with OCD. Together with emerging pharmacological data showing differential responsiveness to treatment of tic-related OCD vs non-tic-related OCD, these data also argue strongly for the incorporation of tic-relatedness as a variable in biological and behavioral studies of patients with OCD.
Adolescent↗
Serotonin and the neurobiology of depression. Effects of tryptophan depletion in drug-free depressed patients.
OBJECTIVE: To investigate the effects of tryptophan depletion in untreated depressed patients. Rapid dietary depletion of the precursor of serotonin synthesis, tryptophan, causes a transient return of depression in 67% of patients who have had a therapeutic antidepressant response. METHOD: Forty-three untreated depressed patients underwent tryptophan depletion in a double-blind, placebo-controlled cross-over study. After testing, they received open sequential antidepressant treatment. RESULTS: Mood did not change when tryptophan was depleted but did change on the day after the depletion test. Relative to the control test, 37% of the patients had 10-point or greater decrease in Hamilton Depression Rating Scale (Ham-D) score, while 23% had a 10-point or greater increase in Ham-D score on the day after the tryptophan depletion test. Change in mood was correlated to treatment response after testing. Patients whose condition worsened proved to be highly refractory to treatment while those who showed improvement were more likely to respond. CONCLUSIONS: That tryptophan depletion did not rapidly worsen depression argues that serotonin function is not linearly related to the level of depression and if reduced serotonin function does cause depression, then it is either as predisposing factor or due to a postsynaptic deficit in the utilization of serotonin.
Adult↗
Decreased perceptual sensitivity to emotion-evoking stimuli in depression.
We measured two aspects of emotional response in depressed patients, as a preliminary study of the potential usefulness of such measures for elucidating pathophysiological mechanisms. First we used electromyography to measure the automatic mimicry on an individual's own face of facial displays of emotion observed on the faces of others. Next we used the fused dichotic listening paradigm to measure selective perception of both positive and negative emotion-related words as opposed to neutral words. Patients failed to show the normal facial mimicry of both positive and negative facial displays, despite normal cognitive processing of the stimuli. They also heard significantly fewer positive and negative words on the dichotic tests than did healthy controls. This suggests that depressed patients are hyposensitive to emotion-related stimuli in general.
Adult↗
The role of central oxytocin in obsessive compulsive disorder and related normal behavior.
Oxytocin (OT) is a neurosecretory nonapeptide synthesized in hypothalamic cells, which project to widely distributed sites in the CNS as well as the neurohypophysis. Central OT affects a variety of cognitive, grooming, affiliative, sexual, and reproductive behaviors in animals. Obsessive Compulsive Disorder (OCD) includes a range of cognitive and behavioral symptoms that bear some relationship to dimensions of behavior associated with OT. Anecdotal data and a recently completed cerebrospinal fluid (CSF) study provide evidence that some forms of OCD are related to OT dysfunction. Based on these findings, we hypothesize: 1) that some forms of OCD are at the extreme end of a range of normal behaviors that are mediated by OT and related systems; and that 2) some normal cognitive, affiliative, and sexual behaviors contain elements that are similar to features of OCD. Alternative hypotheses are considered, and a series of predictions are presented concerning the relationship between central OT and the onset, course, treatment response, and response to challenge procedures seen in this form of OCD.
Animals↗
Buprenorphine: duration of blockade of effects of intramuscular hydromorphone.
Six opioid-dependent in-patients were maintained on daily sublingual doses of buprenorphine at 2, 6, and 12 mg/day for five days at each dose in a randomized, balanced sequence. Placebo buprenorphine was substituted for the next three days, and challenge doses of the mu agonist hydromorphone were administered on the three days. Planned comparisons in a 3-factor ANOVA showed dose-dependent hydromorphone effects, significant blockade of 'high' by the 12 mg buprenorphine dose, and no differences on hydromorphone-induced 'high' across 72 h of active buprenorphine. The data suggest that the blockade by buprenorphine of 'high' persists for at least 72 h after the last dose of buprenorphine.
Administration, Sublingual↗
Neuroendocrine and behavioral responses to intravenous m-chlorophenylpiperazine (mCPP) in depressed patients and healthy comparison subjects.
OBJECTIVE: This double-blind study was undertaken to compare central serotonergic function in depressed patients and healthy comparison subjects by examining neuroendocrine and mood responses to intravenous infusion of the serotonin agonist m-chlorophenylpiperazine (mCPP). METHOD: The participants were 20 drug-free patients with DSM-III-R major depression and 18 healty comparison subjects. After an overnight fast, the subjects received an intravenous infusion of mCPP, 0.1 mg/kg, or placebo saline. Blood was obtained for measurement of serum prolactin, growth hormone (GH), and cortisol. Visual analogue scales were used to assess mood. RESULTS: The depressed patients had a blunted GH response and felt less drowsy than the comparison subjects; prolactin, cortisol, and the remaining behavioral ratings showed no differences between the two groups. CONCLUSIONS: In light of findings with other provocative agents, the blunted GH response to mCPP may reflect a defect in GH production in depression and could be a marker of the depressed state. The lack of differences in the other neuroendocrine variables suggests that the functioning of postsynaptic serotonergic receptors responsive to mCPP may be relatively intact in depression.
Adult↗
Physical symptoms associated with paroxetine discontinuation.
Explore the source record for details and available documents.
Adult↗
Obsessive-compulsive disorder with and without a chronic tic disorder. A comparison of symptoms in 70 patients.
The phenomenological features of 35 obsessive-compulsive disorder (OCD) patients with a lifetime history of tics were compared to 35 age- and sex-matched OCD patients without tics. Seven categories of obsessions and nine categories of compulsions were determined using the symptom checklist of the Yale-Brown Obsessive-Compulsive Scale (YBOCS). Discriminant function analysis revealed that, compared to their counterparts without tics, OCD patients with tics had more touching, tapping, rubbing, blinking and staring rituals, and fewer cleaning rituals, but did not differ on obsessions. These preliminary findings suggest that the types of compulsions present may help to discriminate between two putative subgroups of OCD, i.e. those with and without tics.
Adult↗
Dopamine antagonists in tic-related and psychotic spectrum obsessive compulsive disorder.
Serotonin uptake inhibitors (SUIs) have been established as the first-line pharmacotherapy of obsessive compulsive disorder (OCD). However, approximately one half of patients who receive an adequate trial with these agents remain clinically unchanged. The addition of drugs that enhance serotonin (5-HT) neurotransmission, such as lithium and buspirone, to ongoing treatment in SUI-refractory patients has generally proved to be an ineffective strategy. The addition of dopamine antagonists to the regimens of SUI-resistant patients appears to be a useful approach for OCD patients with a comorbid chronic tic disorder (e.g., Tourette's syndrome) and possibly for those with concurrent psychotic spectrum disorders. These drug response data suggest that both the 5-HT and dopamine systems may be involved in the treatment, and possibly the pathophysiology, of specific subtypes of OCD.
Adult↗
Acute tryptophan depletion in autistic disorder: a controlled case study.
Explore the source record for details and available documents.
Adult↗
m-Chlorophenylpiperazine effects in neuroleptic-free schizophrenic patients. Evidence implicating serotonergic systems in the positive symptoms of schizophrenia.
OBJECTIVE: This study evaluated whether alterations in serotonin function in schizophrenic patients could be demonstrated by comparing the reactivity to a serotonin partial agonist, m-chlorophenylpiperazine (MCPP) in patients and healthy subjects. This study also assessed whether stimulation of serotonin receptors influenced the symptoms of schizophrenia. DESIGN: Double-blind randomized comparison of MCPP (0.1 mg/kg, intravenously, administered over 20 minutes) and placebo effects in patients and healthy subjects. SETTING: Department of Veterans Affairs Medical Center, West Haven, Conn. PATIENTS AND HEALTHY SUBJECTS: Fifteen healthy subjects recruited by public advertisement and 12 schizophrenic inpatients who had been neuroleptic free for at least 2 weeks prior to entry into the study. MAIN OUTCOME MEASURES: The principal outcome variable was the positive symptoms of schizophrenia operationally defined as the sum of scores on the four key items for schizophrenia on the Brief Psychiatric Rating Scale and the Brief Psychiatric Rating Scale thought disorder factor. Anxiety was assessed with a clinician-rated visual analog scale and plasma hormone levels were measured. RESULTS: m-Chlorophenylpiperazine significantly increased the positive symptoms of schizophrenia in patients but not healthy subjects. Patients and healthy subjects exhibited anxiety increases of comparable magnitude following MCPP. However, patients had higher baseline levels of anxiety and exhibited more prolonged anxiogenic responses to MCPP. Anxiety elevations did not correlate with increases in the four key symptoms in patients. Patients exhibited lower baseline prolactin levels compared with healthy subjects, but the two groups did not differ in their prolactin, growth hormone, and cortisol responses to MCPP. CONCLUSIONS: Schizophrenics, the only psychotic patient group studied to date, are the first patient group to exhibit propsychotic responses to MCPP. These data provide further evidence that serotonin systems modulate positive symptoms in some schizophrenic patients.
Antipsychotic Agents↗
Concurrent cocaine-ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene.
Simultaneous abuse of cocaine and ethanol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, has been detected in the urine of patients reporting concurrent use of cocaine and ethanol, and high levels have been found in the blood of victims of fatal drug overdose. This placebo-controlled, double-blind study examined the pharmacokinetic, physiologic, and behavioral effects of dual cocaine and ethanol administration in humans (n = 6). Cocaethylene was found in the plasma only after administration of both cocaine and ethanol, and appeared to be eliminated more slowly than cocaine. Plasma cocaine concentrations were significantly higher during cocaine/ethanol administration. Euphorigenic effects were both enhanced and prolonged, and heart rate was significantly increased, following cocaine/ethanol administration as compared to administration of cocaine or ethanol alone.
Adult↗
Urinary 6-hydroxymelatonin sulfate as a measure of melatonin secretion during acute tryptophan depletion.
The essential amino acid tryptophan (TRP) is the precursor for serotonin (5-HT), which is in turn an intermediary product in the synthesis of melatonin. Acute TRP depletion has recently been shown to decrease nocturnal plasma levels of melatonin in humans. Melatonin is metabolized to 6-hydroxymelatonin sulfate (6-SM), a highly stable end-product which is excreted into urine. To determine the effects of TRP bioavailability on 6-SM, 11 healthy volunteers underwent active and sham TRP depletion in a randomized, double-blind fashion. Samples of plasma free and total TRP, plasma melatonin, and urinary 6-SM were obtained before and after the depletion. Acute TRP depletion decreased free and total plasma tryptophan levels by more than 80% from baseline levels. Nocturnal 6-SM excretion was significantly decreased and highly correlated with decreases in plasma melatonin. These results suggest that nocturnal urinary 6-SM excretion is a valid measure of melatonin secretion under conditions of decreased 5-HT function. Collection of urine for 6-SM is considerably easier than nocturnal plasma sampling for melatonin. Further studies are needed to clarify the relationship between 6-SM excretion and other measures of 5-HT function in neuropsychiatric disorders.
Adult↗
The pharmacotherapy of obsessive-compulsive disorder.
Potent inhibitors of 5-hydroxytryptamine (5-HT) reuptake have clearly been established as the first-line pharmacotherapy for treatment of obsessive-compulsive disorder (OCD). Although a variety of tricyclic antidepressants and monoamine oxidase inhibitors have similar efficacy in the treatment of depression and panic disorder, potent blockade of 5-HT transport appears to be a prerequisite for effective treatment of OCD. Adding agents that enhance 5-HT neurotransmission to ongoing treatment in patients whose OCD is refractory to 5-HT reuptake inhibitors has not yielded impressive results. However, the addition of low-dose dopamine (DA) antagonists to the regimens of treatment-resistant patients appears to be a potentially useful strategy for the specific subgroup of OCD patients with a comorbid chronic tic disorder such as Tourette's syndrome. Because of the toxicity associated with neuroleptics, a time-limited trial of those agents, with reassessment at regular intervals, is indicated. Pharmacologic studies suggest that both the 5-HT and DA systems may be critical to the treatment and possibly the pathophysiology of OCD.
1-Naphthylamine↗