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A case of nonketotic hyperglycemic coma associated with the recent introduction of loxapine is presented. Drug discontinuation led to a return of normal fasting blood glucose. Later challenge with amoxapine was also associated with acute hyperglycemia. Their common metabolite, 7-OH amoxapine, is implicated.

Two patients experienced multiple affective episodes that were consistently preceded by migraine headaches and neurodermatitis. Evidence is reviewed that suggests a possible role for abnormalities of serotonin metabolism for the reported association of affective disorder, migraine, and neurodermatitis.

Levels of 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) were not markedly elevated in a group of 35 panic disorder patients when compared to healthy controls (mean = 2,430 micrograms/day vs. 2,130 micrograms/day). There was a weak association between elevated pretreatment levels of MHPG and a positive treatment response to alprazolam or diazepam. Alprazolam and diazepam may differ in their effects on MHPG.

Neuropsychiatric impairment during senescence and consequent to alcohol abuse demonstrates several parallels in the areas of short-term memory and sensorimotor skills. In this study high-affinity binding of the muscarinic cholinergic antagonist quinuclidinyl benzilate (QNB) was determined with post-mortem human brain tissue from normal young adults, age-matched ethanol abusers, and nondemented senior adults without histories of substance abuse. Hippocampus was chosen because of its high-density cholinergic innervation and probable role in the mnemonic process. A statistical significance emerged between nonalcoholic young adults and both ethanol abusers and seniors in reference to cooperative binding interactions (Hill coefficient, nH) amongst the latter two groups. Analysis of the respective receptor affinities (KD) revealed a significant difference between each group. A trend toward an increased KD occurred from nonalcoholic young adults to alcoholic young adults to nonalcoholic seniors. Concerning the density of receptor sites (Bmax) no difference emerged between alcoholic or nonalcoholic young adults. However nonalcoholic seniors manifest a statistically significant reduction in Bmax; this feature is consistent with the reports of several other investigators. Amongst subjects with a pathologic history of ethanol abuse, a premature senescence along parameters of nH and KD emerged, albeit not including the apparent age-dependent decline in Bmax.

At least 35,000 persons kill themselves each year in the United States. Many of the victims saw their family doctors during the month before death. Suicide assessment and subsequent intervention may help prevent these deaths. Suicidal behavior is associated with alcoholic intoxication and with feelings of hopelessness. Low brain serotonin is under investigation as a possible etiologic factor.

In this in vitro study we investigated the effects of a variety of cations on binding of the cholinergic antagonist, (3H)-quinuclidinyl benzilate, to the human caudate. Physiologic sodium concentrations induced a state of positive cooperativity upon the human muscarinic cholinergic receptor (nHill = 1.41). Lithium at therapeutic equivalency (1 mM) was unique in increasing the dissociation constant (KD) for this antagonist from 35.9 to 72.4 pM. This implies a lithium-induced cholinomimetic effect at the human muscarinic receptor consistent with reports of the reversal of mania by physostigmine. These findings are also relevant to previous cholinergic receptor studies in which various cations have been employed.

A peripheral model offers a valuable research tool for the investigation of central cholinopathic disorders. The in vitro affinities of several psychotropic drugs for the muscarinic cholinergic binding sites of human caudate and erythrocyte were compared in competition with a tritiated antagonist (quinuclidinyl benzilate). The relative affinities of the drugs for both tissues were strikingly similar. Thus, the erythrocyte muscarinic receptor may represent an accessible in vitro assay for the characterization of central cholinopathic states.

The authors analyzed the dexamethasone suppression test (DST) results of 54 patients with major depressive disorder in relation to their pre-DST levels of cholesterol, sodium, potassium, and blood glucose, which are thought to have adrenocorticotrophic links. Discriminant analysis revealed that sodium alone was a significant predictor of nonsuppression. Validation of the predictive power of sodium could minimize the need for DST administration.

A variety of immune phenomena have been associated with chlorpromazine. One such factor, the lupus-like anticoagulant, while nonspecific, has been reported in 26 to 75% of chronic chlorpromazine recipients, although the exact incidence is unknown and requires further investigation. Such patients may have an enhanced risk of bleeding profiles (hemophilia-like) or, conversely, thrombotic events. A case of such a lupus-like anticoagulant with a circulating inactivator of coagulation is discussed in light of the recent literature.

The long-term maintenance of major affective disorders with tricyclic antidepressants is of obvious interest. However, discrete predictors identifying subgroups 'at-risk' for higher recurrence rates have infrequently been cited. The clinical course of 32 major recurrent depressive patients was monitored over 2 years. Analysis of the total tricyclic concentration and the parent: desmethylated ratio revealed that those subjects in a depressive recurrence previously had had a lower imipramine: desipramine ratio (despite matched dosing and nonsignificant total plasma concentrations) than nonrecurrents. Several hypotheses are discussed.

The family physician occupies a critical place in the detection and management of mental health problems. Optimal case management requires an awareness of individual limitations and effective use of a psychiatric consultant. The consultant must understand the unique relationship between the patient and the family physician. Several historical biases may impede the physician's use of psychiatric consultation and the patient's acceptance of psychiatric treatment options.

Treatment response to antidepressant medication was examined in 59 patients with nonchronic major depression and 35 patients with chronic major depression. Patients with chronic major depression had a poorer response to imipramine or desipramine than nonchronic patients.

Myoclonus associated with cyclic antidepressant therapy has been considered to be a rare phenomenon. Ninety-eight patients who were to begin receiving cyclic antidepressant therapy were prospectively evaluated for myoclonus. Thirty patients experienced clinically insignificant drug-associated myoclonus. Nine patients had clinically significant myoclonus. The myoclonus was reversible with the discontinuation of therapy but tended to persist if medication changes were not made. None of the tested clinical variables were able to predict which patients would develop myoclonus.

The spectrum of contemporary antiepileptics are categorically reviewed with reference to adverse behavioral sequelae. These iatrogenic disturbances may have peripheral (eg. heptatic dysfunction, blood dyscrasia, or lupus-like syndromes) or central (eg. altered neurotransmission) manifestations. Whether an idiosyncratic reaction, toxic circumstance, or untoward drug interaction, there is scant understanding of the predisposing factors or recognition of the neuropsychiatric influence of anticonvulsant therapy.

Trazodone has become a very popular second generation antidepressant. In our experience, trazodone levels are frequently obtained albeit interpretation/utility of these levels and purported normal ranges are in question. We analyzed 39 consecutive cases of major depressive disorder treated with trazodone in a primary care medical clinic. Thirty (79%) of subjects had a positive response. While a positive correlation existed between dosage and concentration of the parent drug, no dose-response correlation could be identified within this cohort. However, a minimum level of 250 ng/ml did appear necessary for a response. The overall utility/cost efficacy of second generation antidepressants, in the absence of well designed dose response studies, is questioned.

Current knowledge about monoamine oxidase (MAO) inhibitors is reviewed, with particular attention to the mode of action, prognostic indicators, treatment protocol, response prediction, toxicity, and untoward drug interactions. The MAO inhibitors are often effective in the treatment of affective disorders, anxiety states, and phobias.

Alcoholism is a multifaceted medicosocial problem. Recent literature discusses a common dyad, alcoholism and anxiety. Both disorders are interdigitated with the brain amine serotonin (5-hydroxytryptamine, 5-HT). Direct 5-HT activation reportedly attenuates alcohol consumption, whereas depletion enhances use patterns. Acute alcohol consumption has also been associated with a transient rise, albeit eventual diminished 5-HT turnover. A variety of 5-HT models have confirmed this observation, e.g., reduced platelet 5-HT content, uptake, and cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid. Such altered characteristics of 5-HT secondary to chronic alcohol use may explain the frequent morbidity of anxiety and/or depression. Acute alcohol consumption is also associated with accumulation of the 5-HT aldehyde derivative 5-hydroxymethtryptoline. Thus, alcohol may induce the in vivo formation of aldehydes, e.g., beta-carbolines, that themselves possess high lipophilicity and psychotropic activity. Future investigation into 5-HT-specific pharmacologic probes in alcoholism will be interesting. Preliminary research has consistently demonstrated that 5-HT-enhancing agents (e.g., zimelidine or fluvoxamine) decrease alcohol consumption, preference, and short-term memory decrements. Thus, 5-HT appears to represent at least one common denominator for a spectrum of behavioral disorders including anxiety and alcoholism.

Based on evidence that mania may include an alteration of cholinergic function, we have previously investigated the effects of various monovalent ions on the muscarinic cholinergic receptor from human caudate nucleus utilizing the radio-labeled antagonist (3H)quinuclidinyl benzilate (QNB). In this study we observed that Li+ at 1 mM was unique in its ability to specifically reduce the affinity of 3H-QNB for the muscarinic receptor (increasing the QNB dissociation constant from 35.9 pM to 72.4 pM). The sodium-specific induction of positive cooperativity (nHill) at the muscarinic cholinergic receptor was inhibited in the presence of Li+. Both observations achieved statistical significance at p less than 0.05. A Li+-related decrease in specific QNB binding sites (Bmax) by 23% (from 2480 to 1900 pmole/g protein) was additionally manifest, albeit only achieving a statistical trend (p less than 0.10). The exact mode of Li+ action in the management of major affective illnesses remains speculative. The observations that this cation specifically mediates a reduction of muscarinic receptor affinity and number of binding sites within the human caudate suggests further consideration of the association between muscarinic cholinergic activity and mania as it relates to Li+.

The relationships between several patient variables and lithium dosage requirements were determined in 71 inpatients receiving a slow-release lithium product. Age, weight, ideal body weight, sex, body surface area, creatinine clearance, presence of depression, concurrent use of tricyclic antidepressants, and acuteness of symptoms were significantly related to dosage requirements. The contribution of each factor to dosage requirements was further defined using multiple regression analysis and used to assess a published patient variable-based lithium dosing technique. Addition to that model of information concerning presence of depression, acuteness of symptoms, and creatinine clearance minimally improved predictability. The published model is recommended as an alternative to empiric methods.

Anxiety may be associated with increased norepinephrine activity. Urinary levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) were examined in depressed patients with and without panic attacks. Depressed patients with panic attacks had significant elevations of MHPG.

Atrial flutter developed in an 80-year-old woman after 10 days of treatment with maprotiline at therapeutic concentrations. This cardiac irregularity is extremely rare with the conventional antidepressants. Evidence is reviewed to suggest that the likely mechanism was reuptake blockade of noradrenergic amines stimulating reentrant excitation within the atria.

Four patients with obsessive-compulsive disorder (DSM-III and RDC) were treated in an open trial with alprazolam. Moderate to marked improvement was noted in the degree of obsessionality, anxiety with motor tension, and secondary affective changes. The mixed anxiolytic-antidepressant properties of alprazolam are theorized as the basis for the clinical remissions.

An elderly woman developed a high serum digoxin concentration resulting in toxicity when alprazolam was added to her digoxin therapy. The reduced renal clearance of digoxin is postulated as the mechanism for this interaction.

Postpartum depression (PPD) occurs in 4% of women during the puerperium. Patients with a previous history of depression, especially a postpartum depression, have a much greater incidence of PPD. Those patients should be evaluated carefully during the six-week period following parturition. PPD is to be differentiated from "baby blues," which occur in more than 50% of women postpartum. Baby blues are characterized by intermittent, mild affective symptoms that remit spontaneously after several days.

Hypersomnia was experienced by 17 of 102 patients with major depressive disorder. Comparisons between hypersomnic and non-hypersomnic depressives demonstrated significant associations between hypersomnia and increased appetite, weight gain, agitation, headaches, depression in a first-degree relative, and earlier age of illness onset.