Jerry A. Bennett

Valproate treatment of panic disorder and lactate-induced panic attacks

Several lines of evidence suggest that the anticonvulsant drug valproate may have antipanic properties: (1) It enhances gamma-aminobutyric acid activity in the brain; (2) it has anxiolytic effects in animal models of anxiety; and (3) it has been reported to be effective in panic disorder in several preliminary studies; however, valproate has not been studied in the prevention of lactate-induced panic attacks. Sixteen patients with panic disorder underwent a lactate infusion followed by a 28-day treatment period with valproate and subsequent rechallenge with lactate. Response was measured by change in panic attack frequency and Hamilton Anxiety Scale (HAS) scores and by the ability of valproate to block lactate-induced panic on rechallenge. Of the 14 patients completing the 28-day trial, 10 (71%) experienced a greater than 50% reduction in the weekly frequency of panic attacks. Six (43%) had complete remission. HAS scores dropped significantly from a baseline mean of 30.8 +/- 9.4 (SD) to 12.6 +/- 7 after 4 weeks of treatment. Valproate blocked reinduction of panic symptoms on lactate rechallenge in 10 (83%) of 12 patients who had initially experienced panic symptoms on initial infusion. The significant reduction in spontaneous panic attacks and the blockade of lactate-induced panic symptoms by valproate support earlier studies suggesting that the drug may be an effective treatment for panic disorder.

Anticholinergic serum levels and cognitive performance

SummaryIntegrity of central cholinergic neurotransmission is essential for adequate cognitive functioning. Many psychotherapeutic medications have anticholinergic side-effects. In order to determine the impact of circulating anticholinergic activity on cognitive performance, 28 geropsychiatric inpatients underwent cognitive testing at different levels of anticholinergic serum activity. In 10 subjects with a diagnosis of probable Alzheimers disease, significant deterioration of selected cognitive functions was observed at anticholinergic serum levels that caused no dysfunction in the 18 non-demented subjects. The data suggest that non-demented elderly patients with psychiatric problems tolerate psychotropic pharmacotherapy without significant negative impact on their cognitive competency. By contrast, patients with Alzheimers disease are at risk of additional impairment. The introduction of anticholinergic serum activity as a monitoring technique for safe psychopharmacotherapy in geriatric patients is discussed.

Valproate as a Loading Treatment in Acute Mania

Evidence from earlier studies indicates that the antimanic action of valproate becomes most apparent within 1-4 days of achieving serum concentrations 50 micrograms/ml, that valproate can be orally loaded with achievement of therapeutic serum concentrations within the first several days of treatment, there is a rapid onset of response, and minimal side effects. To provide further data on the safety and efficacy of valproate oral loading in the treatment of acute mania, we evaluated 13 consecutive patients with acute manic syndromes who received valproate initiated at a dosage of 20 mg/kg/day. In most cases, valproate was added to other psychotropics. All 13 patients received at least 5 full days of valproate maintained at or above 20 mg/kg/day, and valproate serum concentrations were 50 micrograms/ml (mean +/- SD = 88 + 25) by the second or third day of treatment. Ten (77%) patients displayed a moderate or marked response. Side effects were infrequent and minor. Consistent with our earlier study, these findings suggest that valproate can be safely administered via a loading dose of 20 mg/kg/day to patients with acute mania, including those on other psychotropics, and that it may produce a rapid response with minimal side effects.

Antiepileptic Drugs for the Treatment of Panic Disorder

Evidence from preclinical studies, preliminary clinical reports, pharmacologic challenge studies and a small number of controlled trials suggests that several antiepileptic agents--valproate, carbamazepine, and clonazepam--may have therapeutic effects in the treatment of patients with panic disorder. We review the theoretical basis and available clinical data supporting the use of these agents in panic disorder.

A Risk-Benefit Assessment of Pharmacological Treatments for Panic Disorder

SummaryPanic disorder, a psychiatric disorder characterised by frequent panic attacks, is the most common anxiety disorder, affecting 2 to 6% of the general population. No one line of treatment has been found to be superior, making a risk-benefit assessment of the treatments available useful for treating patients. Choice of treatment depends on a number of issues, including the adverse effect profile, efficacy and the presence of concomitant syndromes.Tricyclic antidepressants (TCAs) are beneficial in the treatment of panic disorder. They have a proven efficacy, are affordable and are conveniently administered. Adverse effects, including jitteriness syndrome, bodyweight gain, anticholinergic effects and orthostatic hypotension are commonly associated with TCAs, but can be managed successfully.Selective serotonin (5-hydroxytryptamine; 5HT) reuptake inhibitors are also potential first line agents and are well tolerated and effective, with a favourable adverse effects profile. There is little risk in overdose or of anticholinergic effects. Adverse effects include sedation, dyspepsia and headache early in treatment, and sexual dysfunction and increased anxiety, but these can be effectively managed with proper dosage escalation and management.Benzodiazepines are an effective treatment, providing short-term relief of panic-related symptoms. Patients respond to treatment quickly, providing rapid relief of symptoms. Adverse effects include ataxia and drowsiness, and cognitive and psycho-motor impairment. There are reservations over their first-line use because of concerns regarding abuse and dependence.Monoamine oxidase inhibitors, because of their adverse effects profile, potential drug interactions, dietary restrictions, gradual onset of effect and overdose risk, are not considered to be first-line agents. They are effective however, and should be considered for patients with refractory disease.Valproic acid (valproate sodium), while not intensively studied, shows potential for use in panic disorder. More studies are needed in this area before the available data can be confirmed. As a supplement to drug therapy, cognitive behavioural therapy is effective. It is well tolerated, and may be beneficial in certain clinical situations. Its main drawback is the time commitment and effort needed to be made by the patient.

Desmopressin for Risperidone-Induced Enuresis

AbstractWe present a case report which illustrates the successful use of desmopressin for the treatment of risperidone-induced enuresis.

Combined thioridazine and desipramine: early antidepressant response

The authors examined the effect of combined thioridazine (THI) and desipramine (DMI) for an early antidepressant response in 14 patients with a DSM III diagnosis of major depressive disorder with melancholia. All 14 patients received a constant dose of 200 mg DMI/day for 21 days while 7 patients received 100 mg THI/day for only the first 7 days. A significantly greater improvement from baseline Hamilton Depression Scale (HDS) scores occurred during the first 7 days in patients receiving both drugs. Possible mechanisms for this early antidepressant action are discussed.

The costs of treatment of bipolar disorder

From the studies reviewed above, a number of aspects regarding the economic impact of bipolar disorder are clear. First, the cost of this illness in disability and human suffering is profound. Second, the economic cost of the illness far outweighs the costs of treatment. Third, cost savings may differ among the available mood-stabilizing medications, depending on clinical and pharmacological variables. Fourth, the costs of hospitalization contribute the single greatest share of treatment costs, greatly outweighing the costs of drug acquisition. Thus, decisions regarding the inclusion of medications for patients with bipolar disorder on formularies require consideration of the impact of successful treatment on preventing morbidity and mortality, enhancing productivity and preventing hospitalization (Keck et al. 1998b).

A target-dose finding study of clozapine in patients with schizophrenia.

Evidence from recent studies suggests that clozapine plasma concentrations greater than 350 ng/ml are correlated with therapeutic response. However, little is known about the clozapine dosages required to achieve these plasma concentrations. The purpose of this study was to determine if a target dose of 6 mg/kg/day of clozapine would produce a steady state plasma concentration of > 350 ng/ml. Twelve patients with schizophrenia by DSM-III-R criteria who were refractory to treatment with standard antipsychotics were treated with clozapine utilizing a 10- to 14-day titration to a target dose of 6 mg/kg/day. The mean (+/- SD) clozapine plasma concentration achieved after 5 days at the target dose was 584 +/- 417 ng/ml. Thus, although the target dose successfully produced therapeutic plasma concentrations for most patients, a wide variation was also apparent.