Effects of divalproex versus lithium on length of hospital stay among patients with bipolar disorder.

The medical records of all inpatients with bipolar disorder at the Connecticut Mental Health Center in 1997 were examined to compare length of stay for patients who began monotherapy with divalproex (27 treatment starts) and lithium (20 treatment starts). No statistically significant difference was found in length of stay (11. 5+/-6.9 and 10.3+/-5.2 days for patients on divalproex and lithium, respectively) or other length-of-stay variables. Demographic variables, diagnostic variables, and dosages of neuroleptics and benzodiazepines used adjunctively were similar as well. Dosages and blood levels for divalproex and lithium were consistent with practice guidelines. Prospective randomized studies are needed to compare the cost-effectiveness of divalproex and of lithium in the treatment of bipolar disorder.

Effects of lamotrigine on behavioral and cardiovascular responses to cocaine in human subjects.

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.

Interactions of cocaine with nimodipine: a brief report.

This double blind, placebo controlled study of acute calcium channel antagonist use during cocaine administration in five patients found that 60 mg of nimodipine treatment attenuated the systolic, but not diastolic, blood pressure effects of cocaine. In three subjects, a 90 mg dose of nimodipine showed a greater attenuation than that of 60 mg. Subjective effects of cocaine were not altered by either dose of nimodipine.

The effect of lamotrigine on naloxone-precipitated opiate withdrawal.

We hypothesized that lamotrigine, a putative glutamate release antagonist, would attenuate glutamate-mediated signs of opiate withdrawal. Seven heroin-dependent subjects were hospitalized, stabilized on oral levorphanol 6 mg three times daily, and thrice underwent withdrawal precipitated by naloxone 0.4 mg intravenously. Lamotrigine (placebo, 250 mg, and 500 mg) was randomly given as a pretreatment 6 h before naloxone. Lamotrigine did not significantly attenuate any measure of opiate withdrawal. Lamotrigine was well-tolerated in subjects, although one did develop an allergic rash.

Dose dependent effects of yohimbine on methadone maintained patients.

Twelve methadone-maintained patients were randomized into a controlled crossover study with active and placebo yohimbine 20 mg once a day (n = 4), 5mg three times a day (n = 4) or 10 mg three times a day (n = 4) for seven days to evaluate the effect of yohimbine on naloxone precipitated opiate withdrawal. The yohimbine dose of 10 mg TID was well tolerated and was associated with an average decrease of 30% in precipitated withdrawal symptoms.

Effects of gamma-hydroxybutyric acid (GHB) in opioid-dependent patients.

Gamma-hydroxybutyric acid (GHB) is a GABA metabolite used clinically for sleep induction. The abuse liability of GHB is controversial. As part of a study of the effect of GHB pretreatment on naloxone-precipitated opiate withdrawal, eight opioid-stabilized subjects received a balanced, randomized, double-blind sequence of oral placebo, GHB 15 mg/kg and 30 mg/kg. GHB had no consistent physiological effects. After GHB and prior to naloxone, subjects rated "sluggish," "spaced," "carefree," and "good-mood" higher after GHB 30 mg/kg than after placebo. Subjects identified the 30 mg/kg dose as most similar to placebo (n = 3), benzodiazepine (n = 2), opiate (n = 2), and alcohol (n = 1).

Sustained-release methylphenidate for cognitive impairment in HIV-1-infected drug abusers: a pilot study.

Other investigators have reported clinical improvement from psychostimulant drugs in patients with HIV-1-related cognitive impairment. However, no previous research has substantiated this claim by using a controlled study design. We examined the efficacy of sustained-release methylphenidate (MSR) in a sample of substance abusers with HIV-1-related cognitive impairment. Eight HIV-1-infected methadone patients with impaired neuropsychological test performance participated in an inpatient double-blind placebo-controlled crossover trial of MSR 20-40 mg/day. On a composite neuropsychological measure, patients improved significantly from baseline during MSR but not placebo treatment. Nevertheless, MSR performance did not differ significantly from placebo performance. Patients appeared to improve as a function of time, regardless of sequence, with somewhat more improvement during MSR than placebo treatment.

A pilot study of dextromethorphan in naloxone-precipitated opiate withdrawal.

Dextromethorphan and its metabolite dextrophan antagonize N-methyl-D-aspartate (NMDA)-mediated activity in pre-clinical studies. We examined dextromethorphan's effects on naloxone-precipitated opiate withdrawal in opiate-dependent subjects stabilized on 25 mg of methadone. Subjects received challenges on three different days with 0.4 mg of intramuscular naloxone. Pretreatment 1 h before naloxone was with dextromethorphan in a double-blind, balanced, randomized design with either placebo, dextromethorphan 60 mg, or dextromethorphan 120 mg for six subjects; and placebo, dextromethorphan 120 mg, or dextromethorphan 240 mg for five subjects. There was considerable inter-individual variability in the response to dextromethorphan, but no net attenuation by dextromethorphan on any withdrawal measure assessed. Two of three subjects detoxified from methadone with dextromethorphan 60 mg orally every 4 h demonstrated considerable withdrawal.

Effect of clonidine pretreatment on naloxone-precipitated opiate withdrawal.

The purpose of this pilot study was to validate a methodology for testing the opioid withdrawal-attenuating effects of new medications using clonidine as a positive control. Seven heroin-dependent subjects stabilized on levorphanol received naloxone challenge tests on 4 consecutive days in a 2 x 2 design with placebo or clonidine (0.4-0.5 mg) pretreatment, followed by 0.2 or 0.4 mg of i.v. naloxone. The change in the area-under-the-curve from the preclonidine base line for various measures of withdrawal was analyzed in a two-factor (naloxone dose and clonidine condition) analysis of variance. Clonidine significantly (P < .05) attenuated systolic and diastolic blood pressure, pulse, lacrimation, nasal congestion and plasma cortisol, but not subject-rated withdrawal severity. There was a robust dose-dependent adrenocorticotropic hormone response to naloxone that was not changed by clonidine pretreatment. The consistency between these results and prior studies of clonidine's antiwithdrawal efficacy suggests the validity of the methodology for testing medications to treat opiate withdrawal. Studies with larger samples are needed to refine this methodology.

The effect of gamma-hydroxybutyric acid on naloxone-precipitated opiate withdrawal.

Because gamma-hydroxybutyric acid (GHB), a GABA metabolite, attenuated spontaneous opiate withdrawal in a prior study, we studied GHB's effect on naloxone-precipitated opiate withdrawal. Eight opiate-dependent inpatients were stabilized on the opioid levorphanol, 18 mg daily. After an initial acclimatization challenge, subjects underwent three double-blind challenges on consecutive days. Pretreatment in a balanced randomization was with either placebo, GHB, 15 mg/kg, or GHB, 30 mg/kg, followed an hour later by intravenous naloxone, 0.4 mg/70 kg. GHB produced no significant attenuation of multiple withdrawal measures except for hot-cold feelings. GHB pretreatment slightly accelerated respiration prior to naloxone. Differences with prior studies may be due to (1) timing of GHB administration (giving postwithdrawal in prior studies), (2) direct reversal of GHB's anti-withdrawal effects by naloxone, or (3) differences between naloxone-precipitated and spontaneous opiate withdrawal.

Reliability of sequential naloxone challenge tests.

To determine the reliability of serial naloxone challenges, five heroin addicts stabilized on methadone were given 0.2 mg naloxone intravenously on three consecutive days. Two-factor ANOVA revealed that the between-subjects effect accounted for at least 63% of the variance in each of the dependent measures, and the effect of challenge number for at most 22%. Withdrawal tended to be slightly more severe for the first challenge. Intraclass correlation coefficients were calculated for the area-under-the-curve of the change from baseline: subject-rated (.74) and observer-rated (.71) withdrawal, pulse (.88), systolic blood pressure (.58), diastolic blood pressure (.85), and skin temperature (.63).

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.

Neuroleptic exposure following inpatient treatment of acute mania with lithium and neuroleptic.

The authors examined continued neuroleptic exposure following inpatient treatment of mania with neuroleptics and lithium through structured chart review of 40 consecutive patients. At discharge, patients were receiving a mean of 793 mg/day (SD = 695) chlorpromazine equivalents; 6 months later they were receiving a mean of 634 mg/day (SD = 684). This decrease was statistically significant, but the patients' ongoing neuroleptic exposure remained substantial.

Effects of acute buprenorphine on responses to intranasal cocaine: a pilot study.

Five inpatients dependent on both intravenous cocaine and heroin were detoxified from opiates. They were then given 5 days of double-blind treatment with active or placebo buprenorphine 2 mg/d sublingually, followed by a crossover to the converse for 5 days (buprenorphine or placebo). Intranasal cocaine challenges (2 mg/kg) were performed on Days 3 and 5 of each treatment. Buprenorphine significantly enhanced patients' ratings of cocaine-induced pleasurable effects, and augmented cocaine-induced pulse increases. The buprenorphine enhancement of subjective cocaine effects appeared to be more prominent on Day 3 than on Day 5. This reduction from Day 3 to Day 5 suggests that cocaine may interact differently with buprenorphine as treatment is more prolonged.

What's new in laboratory testing procedures for psychiatrists?

The potential uses of the laboratory in psychiatric diagnosis and treatment expanded greatly over the decade of the 70s. This paper focuses on some of the newer areas of neurobiological research that may become clinically available to psychiatrists during the decade of the 80s. Research on state markers such as platelet serotonin and MAO levels, CSF metabolites, endorphins, MHPG, TRH and DST is discussed, followed by information on possible trait markers such as HLA gene typing, red blood cell membranes, and beta adrenergic receptor assays. Through these areas of study it is hoped that there will come more accurate psychiatric diagnosis and improved response to treatment.