Charcoal enhancement of treatment for tricyclic-induced mania.

Induction of mania by tricyclic antidepressants (TCAs) is controversial, with indirect evidence for and against it. Unusual direct evidence of it was observed in a 77-year-old female patient having ingested an amitriptyline overdose. Mania developed while the TCA blood levels were high, and responded to a combination of charcoal and valproate. However, mania reappeared when charcoal was discontinued, and disappeared again when it was restarted. This time course suggests a therapeutic advantage for adding charcoal to valproate in treating tricyclic-induced mania. Presumably, charcoal might have removed a mania-inducing metabolite of amitriptyline. Moreover, repeated doses of oral activated charcoal accelerated the elimination of TCA from the blood stream to several times its original rate, which is consistent with interruption of the enterohepatic circulation. This enhanced elimination and improved outcome illustrate the value of repeated charcoal doses after TCA overdose, and suggest its use when mania develops in a patient who takes an antidepressant, at least amitriptyline or nortriptyline.

Long-term outcome after ECT for catatonic depression.

INTRODUCTION: This is the initial report of the course of major depression with catatonic features after hospitalization. METHOD: Telephone interviews and ratings were conducted 3-7 years after response to inpatient electroconvulsive therapy (ECT) for such catatonic depression. This was done for all 19 followable patients treated over a particular 4-year period. All had received left anterior right temporal brief-pulse ECT. Prior to data examination, we constructed rules to classify medications as antimelancholic. These rules led to the inclusion of lithium, tricyclics, bupropion, and venlafaxine in this antimelancholic classification and to the exclusion of selective serotonin reuptake inhibitors. RESULTS: Ten of the 13 patients discharged on antimelancholic medication (AMM) had good function on follow-up and no more than one rehospitalization. In contrast, none of the six patients in the other group had as good an outcome (p = 0.004, corrected chi2 = 8.26). The AMM group had no deaths, but three patients in the other group died of acute cardiopulmonary causes (p = 0.015). In most cases, catatonia and depression were not identified by informant interview on follow-up. DISCUSSION: ECT followed by AMM usually led to long-term outcome that was good and better than without such medication. Although benzodiazepines can acutely diminish catatonia, we found no relevant long-term study; accordingly, long-term benzodiazepine use in catatonia is speculative.

Melancholic symptoms during concurrent olanzapine and fluoxetine.

The concomitant use of olanzapine and fluoxetine has been advocated for the treatment of various psychiatric disease states. We describe a case in which the combination of olanzapine and fluoxetine appears to have caused the psychopathology of melancholic depression requiring hospitalization in a 40-year-old female. Postulated mechanisms for this drug interaction, particularly CYP450 isoenzyme inhibition by fluoxetine, is discussed.

Efficiency of the stimulus characteristics of ECT.

OBJECTIVE: Greater ECT stimulus efficiency allows for a lower stimulus dose and should diminish the side effects of ECT. METHOD: Four different ECT stimuli of identical charge (average mC=2.5 times age) with pulse widths of 0.5 msec and 1 msec and frequencies of 30 Hz and 60 Hz, respectively, were compared for efficiency. The stimuli were applied in a balanced order to each of 24 subjects. Asymmetric bilateral electrode placement was used. RESULTS: Peak heart rates were higher with the 0.5-msec pulse width than the 1-msec pulse width. Seizure induction was more successful with the 0. 5-msec pulse width than the 1-msec pulse width. Stimulus frequency had no effect on heart rate or seizure induction. CONCLUSIONS: The pulse width of 0.5 msec is more efficient than the 1-msec pulse width. The "half-age" dose for the first bilateral ECT treatment is usually successful for subsequent ECTs when the 0.5-msec pulse width is used.

Physiological response to ECT stimulus dose.

For a physiological effect to be useful to regulate the electrical stimulus dose used in electroconvulsive therapy (ECT), it must show sensitivity to the stimulus dose. In the analogy of using blood drug concentration to regulate drug dosage, this concentration must be sensitive to the dose. Accordingly, we examined the sensitivity of several physiological effects to ECT stimulus dose. Previously no substantial sensitivity of physiological effects was found when generally effective ECT methods were used. EEG post-ictal suppression, recruitment phase duration, wave form regularity and spike-and-wave frequencies, peak seizure heart rate (HR), and several types of seizure duration were measured with standard and higher dose stimuli given on separate days to 24 subjects. Left frontal to right temporal asymmetric bilateral stimulus placement was applied. Peak HR (P=0.007, t=2.7) and EEG recruitment phase duration (P=0.04, t=1.9) varied with stimulus dose, by 12 beats/min and 1.3 s, respectively. Only peak HR (P=0.02, t=2.2) varied with stimulus dose (by 6 beats/min) when subjects who showed only EEG seizure but no motor seizures were excluded. Subjects who maintained peak HR near their individual maximum values received fewer ECTs than other subjects (P=0.00003, t=5.20); this greater efficacy suggests that the peak HR reflects clinical efficacy as well as stimulus dose. In addition to EEG measurements, peak HR is a candidate to measure ECT seizure quality and provide feedback for stimulus dose regulation.

Variations of peak and baseline heart rates.

The heart rate (HR) rises rapidly with ECT seizure onset and falls with seizure termination. The peak HR is a potential reflection of the intensity of the seizure. Because it varies greatly among patients, comparison with a benchmark HR for each patient should be useful. By comparing variations in the peak and baseline HRs, this study aims to determine if the peak HR should be compared with the baseline. HRs were measured on all treatments for 24 subjects receiving asymmetric bilateral ECT, excluding treatments with motoric seizure duration under 18s or no EEG postictal suppression. The resulting mean variations within subjects were significantly larger for the baseline (7.7 bpm, 8.1%, SD 4.6 bpm, p = 0.004 2-tail, p = 3.2 than the peak HR (4.6 bpm, 3.0%, SD 2.4 bpm). This indicates that comparison of the peak HR with the baseline substantially increases random variations. There was a general absence of correlation between peak and baseline HRs; this reveals no rationale for subtraction of the baseline from the peak. An expression of the peak HR that allows comparisons between patients but avoids the baseline HR is the difference between the seizure peak HR and the highest peak HR seen during that patient's ECT course.

Endpoint of ECT-induced elevation in heart rate.

Changes in the heart rate during electroconvulsive therapy (ECT) reflect seizure activity at a deeper brain site than shown by electroencephalography and motoric activity. Accordingly, such changes may provide additional information that is helpful in the evaluation of treatment quality. One basic measurement of heart rate change is the duration of ECT-induced tachycardia. In a prospective study, the electrocardiographic ECT records of 24 patients were rated for the abruptness of the endpoint of the seizure-induced elevation in heart rate; 19 showed abrupt endpoints and 5 showed gradual endpoints. The baseline heart rate of patients with abrupt endpoints (88 SD [standard deviation] 10 beats/min) was significantly lower (p = 0.00001) than those with gradual endpoints (118 SD 12 beats/min). A threshold occurred at a baseline heart rate of 100 beats/min, with abrupt endpoints below and gradual endpoints above. The data suggest that patients with low baseline heart rates might be likely to show bradyarrhythmia during the treatment, and corresponding precautions might be considered.

Is episodic obsessive compulsive disorder bipolar? A report of four cases.

Several reports have noted cases of OCD which were unusual in showing an abrupt remission. We report longitudinal clinical observation of four cases of acute onset OCD without major depression through a variety of treatments. These patients had prominent feelings of shamefulness; compared to patients with typical OCD they were ill for months rather than years and were older. Two had previous episodes of psychiatric illness with full recovery. Full and persistent recovery occurred in response to lithium or an acute course of ECT but not to tricyclic or SSRI antidepressants. The generalizability of these observations is limited by its uncontrolled nature and the small numbers. The courses observed were consistent with episodic OCD as a possible expression of bipolar disorder and consideration of corresponding treatments. This perspective offers a new rationale for reported observations of remissions of acute onset OCD in response to lithium without lithium effectiveness for typical OCD.

Betaxolol in anxiety disorders.

Betaxolol, a long-acting beta-adrenergic blocker that enters the central nervous system, was examined for therapeutic effects on the persistent anxiety of anxiety disorders. Prior studies of beta-blockers examined only agents that were short-acting or did not enter the brain. Betaxolol was administered to 31 patients in open trials. Of 13 outpatients, 11 had generalized anxiety disorder (GAD) and 2 had adjustment disorder with anxiety. Five with GAD had concurrent panic disorder. Of 18 inpatients, 16 had GAD and 2 had adjustment disorder with anxiety. Betaxolol doses were increased until the patient responded or declined further dosage. Severity was rated on a 4-point global scale. Before betaxolol, all were moderately or severely ill. In all patients with panic disorder panic attacks stopped within 2 days (p<0.001). Anxiety decreased to no more than marginally ill in 85% of outpatients (p<0.0001) and all inpatients (p<0.0001). Betaxolol doses were usually 5 mg once or twice daily; four inpatients took 10 to 20 mg twice daily. In sum, betaxolol administration was rapidly followed by improvements that were easily noticed by the doctor, even in patients with longstanding anxiety and obsessive-compulsive personality disorder. Preliminary observations in posttraumatic stress disorder are similar.

Melancholia with onset during treatment with SSRIs.

A defined group of medical records was surveyed for patients who showed onset of major depression with melancholic features while taking an antidepressant medication. Nine cases resulted. In all the antidepressants being taken while melancholia began were SSRIs and the melancholic depression remitted rapidly with the first treatment given, bupropion in five males, nortriptyline with triiodothyronine in two females, and ECT in one male and one female. This suggests that patients who take SSRIs and are melancholic respond well to bupropion, nortriptyline, or ECT. These observations complement reports of low responsivity of melancholic depression to SSRIs and distinctions between melancholic and nonmelancholic depressions.