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The current study assesses the relationship between presenting symptomatology of the self-labeled Hispanic popular diagnosis of ataques de nervios and the specific co-morbid psychiatric diagnoses. Hispanic subjects seeking treatment at an anxiety disorders clinic (n = 156) were assessed with a specially designed self-report instrument for both traditional ataque de nervios and panic symptoms, and with structured or semistructured psychiatric interviews for Axis-I disorders. This report focuses on 102 subjects with ataque de nervios who also met criteria for panic disorder, other anxiety disorders, or an affective disorder. Distinct ataque symptom patterns correlated with co-existing panic disorder, affective disorders, or other anxiety disorders. Individuals with both ataque and panic disorder reported the most asphyxia, fear of dying, and increased fear during their ataques. People with ataques who also met criteria for affective disorder reported the most anger, screaming, becoming aggressive, and breaking things during ataques. Ataque positive subjects with other anxiety disorders were less salient for both panic-like and emotional-anger symptoms. The findings suggest that (a) ataque de nervios is a popular label referring to several distinct patterns of loss of emotional control, (b) the type of loss of emotional control is influenced by the associated psychiatric disorder, and (c) ataque symptom patterns may be a useful clinical marker for detecting psychiatric disorders. Further study is needed to examine the relationship between ataque de nervios and psychiatric disorders, as well as the relationship to cultural, demographic, environmental, and personality factors.

Objective: This field trial was designed to answer four questions. First, are patients presenting with anxious or depressed symptoms that are associated with significant impairment but do not meet DSM-III-R definitional thresholds for axis I anxiety or mood disorders? Second, is the impairment experienced by these patients simply the consequence of the severity of their medical conditions? Third, what percent of these patients present with depressive symptoms only, anxious symptoms only, and a mixture of both? Fourth, how should the operational criteria for the syndrome(s) presented by these patients be defined?, Method: A total of 666 patients from five primary care medical sites and two outpatient mental health sites were administered a semistructured psychiatric interview., Results: Patients presenting with affective symptoms that did not meet definitional thresholds for DSM-III-R axis I disorders were at least as common as patients with several of the already established anxiety and mood disorders in each of the seven sites, and their disorders were associated with significant distress or impairment. A nonspecific pattern of anxious and depressed symptoms was the modal presentation among these patients with currently subdefinitional threshold disorders, and they could be significantly differentiated in terms of current symptoms from patients presenting with a principal diagnosis of generalized anxiety disorder, major depressive episode, or panic disorder with agoraphobia., Conclusions: The authors recommend that a mixed anxiety-depression category be included in the DSM-IV appendix for proposed diagnostic categories that need further study. A criteria set is proposed.

DSM-IV is provisionally including a category of mixed anxiety and depression for several reasons. First, it will be included in ICD-10, and therefore used worldwide. The ICD-10 category and the mixed anxiety and depression category now being included in the appendix of DSM-IV are subsyndromal in that they include patients with both anxious and depressive symptoms that fail to meet criteria for an established anxiety or depression diagnosis. Primary-care physicians regularly report a high incidence of patients whose symptoms fit this subsyndromal definition of mixed anxiety and depression. Such patients are not easily classifiable using DSM-III or DSM-III-R criteria, yet they often manifest sufficient distress and/or disability to require treatment. Those who oppose establishing the diagnosis of mixed anxiety and depression make the following points: (1) patients considered eligible for this diagnosis will actually meet criteria for a current DSM disorder; (2) mixed anxiety and depression will become a "wastebasket" category for a heterogeneous group of patients; (3) if any new subsyndromal diagnosis is needed, minor depression should suffice; and (4) mixed anxiety and depression will overlap extensively with adjustment reaction.

Background: Many investigators have reported that panic disorder (PD) patients with comorbid major depression (MD) have more severe symptoms and a poorer response to treatment than patients with PD alone. It is not known if this is due to a distinct and more serious underlying disorder in these patients or simply a result of the simultaneous presence of the two disorders., Method: Nondepressed patients presenting for treatment of panic disorder with agoraphobia (PDA) were studied before treatment (N = 180) and after 4 weeks of treatment with adinazolam sustained release (N = 89) or placebo (N = 91). Twenty-nine percent (N = 53) of the patients had a past history of MD. Symptom severity and treatment outcome were compared in patients with primary, secondary, single, recurrent, or no past MD., Results: There were no consistent differences in symptom severity or treatment outcome in patients with a past history of primary, secondary, or single episode MD compared with patients with no history of MD. However, a small number of patients with history of recurrent MD exhibited consistently greater symptom severity and poorer response to treatment than patients with no history of MD., Conclusion: The greater severity and worse outcome of comorbid PD and MD observed in earlier studies are more likely due to the simultaneous presence of the two disorders than to a more serious and enduring underlying disorder. However, our results suggest that recurrent MD may indicate a more serious condition in patients with PDA. This possibility warrants further study.

Some forms of anxiety and affective disorder, such as panic disorder and major depression, appear distinct, but frequently symptoms of depression and anxiety occur together. The comorbidity of anxiety and depression not only has implications for the differential diagnosis of the disorder but affects the severity and course of illness and its responsiveness to treatment. The results of studies of atypical depression suggest that this form of depressive illness responds better to monoamine oxidase inhibiting medications than to tricyclic antidepressant agents, and this preferential responsiveness may in fact define the boundaries of atypical depression. The serotonin selective reuptake inhibitor paroxetine seems to have a beneficial effect on symptoms of anxiety and agitation in depressed patients. Further clinical research is needed, however, to determine the best way to manage depression with anxiety and atypical depression.

We report six cases of rapid mood cycling induced by antidepressant treatment. The key to effective treatment involved the recognition of the pattern of apparent remission, relapse, antidepressant and/or stimulant adjustment, remission, relapse, etc. Hypomanic episodes were frequently mild and could be mistaken for remission. The destabilizing effects of antidepressant drugs were not corrected by the addition of mood stabilizers, necessitating the withdrawal of the antidepressant agent. All but one case responded to such withdrawal. Two cases required the addition of high-dose L-thyroxine for stabilization. Implications for an effective treatment protocol are discussed.

Background: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments., Method: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine., Results: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine., Conclusion: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.

Some forms of anxiety and affective disorder, such as panic disorder and major depression, appear distinct, while other forms, such as generalized anxiety disorder and chronic depression or dysthymia, may lie on a continuum and blend with each other. However, even panic disorder and major depression have many common features. Moreover, for reasons not yet clear, they occur together frequently, and their combined occurrence in the same patient has been associated with greater severity and chronicity, decreased treatment responsiveness, and, possibly, increased familial prevalence of anxiety and/or depression. Finally, studies of primary care patients suggest the frequent occurrence of a mixed anxiety-depressive disorder that may often be subsyndromal by DSM-III-R criteria but is nevertheless associated with prominent distress and/or impairment.

We investigated the antidepressant efficacy of l-deprenyl (selegiline), a selective monoamine oxidase B inhibitor (MAOI), in a six-week open trial of 17 patients with atypical depression. Such patients have previously been shown to benefit from nonselective MAOIs such as phenelzine sulfate. Ten patients (59%) responded to l-deprenyl, but nine required dosages above the 10 to 20 mg/day used in previous investigations. l-Deprenyl was superior to six weeks of placebo administered to diagnostically similar patients in a separate double-blind study. In contrast with previous findings with pheneizine, responders to l-deprenyl differed from nonresponders by having lower baseline anxiety ratings. Even at high dosages, there appeared to be fewer side effects with l-deprenyl than with nonselective MAOIs.

A previous study reported that unipolar depressives excrete significantly lower amounts of urinary tyramine-O-sulfate following oral administration of a tyramine hydrochloride load than do normal control subjects. This study replicates and extends those findings by showing that within the heterogeneous group of unipolar depressives, patients with melancholia and bipolar patients with a history of melancholia manifest a tyramine excretion deficit. A small subgroup of medication-free patients in remission from episodes of melancholia had abnormally low tyramine sulfate excretion levels while they were euthymic, supporting the suggestion that reduced tyramine sulfate excretion following oral tyramine loading is a trait marker for depression. Further study of the role of trace amines in affective illness is warranted. Clinical application is not warranted until further evaluation of the sensitivity, specificity, and reproducibility of this oral tyramine challenge test.

Sixty patients meeting specific criteria for atypical depression completed 6 weeks of double-blind, randomly assigned treatment with phenelzine, imipramine, or placebo. Patients who had a history of spontaneous panic attacks or hysteriod dysphoric features showed extremely low placebo-response rates, moderate responses to imipramine, and high rates of response to phenelzine. Conversely, patients without such features responded moderately well to all three treatments. Based on preliminary data, MAOI-specific atypical depression does appear to exist, although in more delimited forms than previously recognized.

An algorithm for transcribing Research Diagnostic Criteria diagnoses for depressive disorders to similar categories in the DSM-III was applied to 103 depressed outpatients previously diagnosed by Research Diagnostic Criteria. All had Hamilton Depression Rating Scale scores of 18 or less. Among 64 patients completing a six-week, double-blind study comparing desipramine hydrochloride with placebo, desipramine was significantly more effective than placebo in patients with DSM-III major depression but not in those with dysthymic disorder. Among patients with major depression, a significant drug-placebo response difference was demonstrated even in those without melancholia. These findings support the clinical usefulness of the DSM-III in the treatment of depressed outpatients. Independent of DSM-III diagnosis, however, evidence of panic attacks seemed to identify patients who benefited from desipramine therapy. This suggests that the DSM-III hierarchy, which excludes consideration of panic in patients with major depression, may require revision.

Sixty patients meeting specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 67% with phenelzine, 43% with imipramine, and 29% with placebo. At week 6, phenelzine was superior to placebo on many measures, while the superiority of imipramine to placebo was confined to several variables. Phenelzine was superior to imipramine on the interpersonal sensitivity and paranoia factors of the 90-item Hopkins Symptom Checklist, with trends toward superiority on several other measures, while imipramine was not differentially superior on any measure. Atypical depressive patients with a history of spontaneous panic attacks and hysteroid dysphoric patients both showed extremely low rates of response to placebo and high rates of response to phenelzine. Conversely, those without panic or hysteroid dysphoric features responded equally to all three treatments. Responders to pheneizine also had greater platelet monoamine oxidase inhibition while receiving drug therapy than did nonresponders. Completion of the 120-patient sample will allow more detailed analyses.

Psychopharacologist have had a longstanding interest in identifying a depressive subtype which selectively benefits from monoamine oxidase inhibitors (MAOIs). A superior rate of improvement with MAOI treatment might help delineate a depressive subgroup with pathophysiology different from other depressive syndromes. Research is described which indicates that patients with reactivity of mood, as well as two of four associated features (hypersomnia, overeating, lethargy, and rejection sensitivity), may have a preferential response to phenelzine as compared with imipramine or placebo. Preliminary data are presented to suggest that patients with reactive mood and only one associated feature may have a preferential response rate to phenelzine compared to imipramine and placebo. Data on patients with reactive mood but no associated features are insufficient at this point to draw any conclusions.

Forty-seven nonmelancholic depressed outpatients were infused with sodium lactate to explore the relationship between history of panic attacks and lactate-induced panic. Lactate panic was rated without knowledge of history of panic. Fifteen of 29 patients (52%) with a history of spontaneous panic experienced panic attacks in response to lactate. Only 1 of 18 patients (6%) without a history of spontaneous panic experienced a lactate-induced panic attack--a highly significant difference. The likelihood of lactate panic was related to frequency of spontaneous panic attacks. The implications of these findings for understanding the relationship of panic attacks and depression are discussed.

Urinary phenylacetic acid (PAA) excretion was found to be decreased in a group of chronic schizophrenic patients, particularly in a nonparanoid subtype. No significant change in PAA excretion was observed in a group of 21 unipolar depressed patients. Urinary PAA was studied following the administration of phenylethylamine, monoamine oxidase inhibitors, a dopa decarboxylase inhibitor, a low phenylalanine diet, and phenylalanine loads in several groups of psychiatric patients and normal volunteers. While Phenylethylamine ingestion increased urine PAA, inhibition of both phenylethylamine metabolism and synthesis failed to alter urine PAA. These studies suggest that urine PAA is primarily derived from phenylalanine transamination or pathways not involving monoamine oxidase or both. The observed decrease in PAA excretion in some schizophrenic patients may reflect an alteration in this pathway. The high phenylethylamine excretion previously reported in some chronic schizophrenic patients is not directly related to the observed low PAA excretion. Therefore measurement of urine PAA is not expected to be useful in assessing any phenylethylamine abnormalities in psychiatric disorders. The possible contribution of reduced phenylalanine transamination and its subsequent increased availability for the possible synthesis of phenylethylamine in schizophrenia is discussed.

34 patients who met the research diagnostic criteria for major depressive disorder as defined by Spitzer et al. [Archs gen. Psychiat. 35: 773-782, 1978] completed a double-blind 6-week trial of mianserin versus amitriptyline following 1 week of single-blind placebo washout. After 2 weeks of dose build-up, patients took 150 mg/day of mianserin or 300 mg/day of amitriptyline throughout the next 4 weeks. At week 6, 63% of mianserin patients and 73% of amitriptyline patients were rated as responders; this difference is not statistically significant. No clinically meaningful differences between drugs were observed with respect to number or severity of side effects as reported by either patient or physician. Overall, mianserin was found to be equivalent to amitriptyline in terms of efficacy, patient tolerance and ease of administration.

Sixty patients with probable atypical depression--defined as meeting Research Diagnostic Criteria for depressive illness, having reactive mood, and having one of four associated symptoms (hyperphagia, hypersomnolence, leaden feeling, and sensitivity to rejection)--took part in a study contrasting phenelzine, imipramine, and placebo. Phenelzine was found to be superior to imipramine and placebo. These results were compared to results from a sample of 120 patients with identical characteristics, except that they had more than one associated atypical symptom (full atypical syndrome). The size of the drug effect was comparable in patients with full atypical and partial atypical syndromes.

Endogenously depressed inpatients often fail to release cortisol following intravenous (i.v.) amphetamine, unlike nondepressed control subjects. We therefore assessed the ability of i.v. dextroamphetamine, 0.15 mg/kg, to induce cortisol release in 64 depressed outpatients diagnosed according to Research Diagnostic Criteria (RDC). After dextroamphetamine challenge, more patients with major depression failed to release substantial cortisol (30%) than those without major depression (5%). Major depressives with endogenous subtype failed to release cortisol (38%) more frequently than those without endogenous depression (23%), but this difference was not significant. After baseline cortisol, sex, and weight loss were controlled for in a regression analysis, however, RDC diagnosis of major depression or endogenous subtype did not account for significant additional variance in cortisol release. In outpatients, abnormal cortisol response to amphetamine may be more closely related to baseline cortisol, sex, and history of weight loss than to RDC subtype of depression.

To examine the biochemical effects of 10-30 mg/day L-deprenyl, measurement of 24-hr urinary output of phenylethylamine (PEA), 3-methoxy 4-hydroxy phenylethyleneglycol (MHPG), and L-deprenyl's amphetamine metabolites were carried out before and during the treatment of atypical depressives. Platelet monoamine oxidase (MAO) activity was also assessed. With L-deprenyl 10-30 mg/day, the expected MAO B inhibition occurred, as indicated by significant increase in urinary PEA excretion and virtual disappearance of platelet MAO activity. Twenty-five to 33% of the daily dose of L-deprenyl was recovered as urinary methamphetamine or amphetamine. Excretion of MHPG was significantly decreased with L-deprenyl 10-20 mg/day. Overall, the results suggest that L-deprenyl's antidepressant effects are mediated by some mechanism other than, or in addition to, MAO B inhibition.

The efficacy of desipramine for mild depression was tested in a double-blind, placebo-controlled study of outpatients with scores below 19 on the Hamilton Rating Scale for Depression (HAM-D). Of 103 such patients, 23 dropped out and 16 improved during a ten-day placebo period. Among 64 patients completing the randomized portion of the study, significantly more improved with desipramine that with placebo. The Research Diagnostic Criteria (RDC) category of major depressive disorder largely accounted for the drug-placebo response difference found for the entire sample. Patients with intermittent depressive disorder improved significantly less frequently with desipramine than patients with major depressive disorder. Independent of RDC diagnosis, severity of illness correlated with outcome. Thus, patients with pretreatment HAM-D scores at or above the median demonstrated significant drug effect, while patients with lower pretreatment HAM-D scores did not.

This study was designed to test the hypothesis that there are 2 biochemical subgroups of 'endogenously' depressed patients--serotonin-deficient and noradrenalin-deficient groups--which respond differently to antidepressants depending on relative blockade of serotonin vs. norepinephrine (NE) reuptake. Patients with pervasive anhedonia and autonomy of depressed mood (endogenomorphic depressives) were treated first with the noradrenergic agent desipramine (DMI), then, if still depressed, such patients were randomized double-blind to continued DMI or clomipramine (CMI), a primarily serotonergic agent. Of 34 such endogenomorphically depressed patients 2 responded during a placebo period and 5 dropped out. Of 27 patients completing at least 4 weeks of DMI (mean maximum daily dose 283 mg, range 100-400 mg/d), 23 (85.2%) responded. With only 4 nonresponders, the second, or CMI, part of the study had to be abandoned. Since DMI strongly blocks neuronal reuptake of catecholamines with little effect on serotonin reuptake, these results suggest that endogenomorphic depressives may have a relatively homogeneous catecholamine deficiency. Alternatively, DMI may exert its effect by a mechanism other than blockade of EN reuptake. Eleven of the endogenomorphically depressed patients also met Research Diagnostic Criteria for situational depression (reactive). Ten of these 11 responded to DMI suggesting that presence or absence of a precipitant may be irrelevant in predicting response to tricyclic antidepressants in endogenomorphic depressions. Mean blood levels drawn at equivalent DMI dose were 238 ng/ml (range, 48-712) for responders, and 352 ng/ml (range, 160-877) for non-responders, indicating that patients appear to respond to DMI across a wide range of blood levels and suggesting the absence of a narrow therapeutic window.

One hundred nineteen patients who met specific criteria for atypical depression completed six weeks of double-blind, randomly assigned treatment with phenelzine sulfate, imipramine hydrochloride, or placebo. The overall response rates were 71% with phenelzine, 50% with imipramine, and 28% with placebo. Phenelzine was widely superior to placebo and also showed superiority to imipramine. Phenelzine superiority appeared even greater after an additional six-week continuation phase. Imipramine was only moderately effective in this atypical depressive sample. Unexpectedly, the superiority of either phenelzine or imipramine to placebo was largely confined to patients in subsets of the study sample who were prospectively judged to also have a history of spontaneous panic attacks and/or show hysteroid dysphoric features. This is consonant with some but not other recent findings and requires replication. Overall, the concept of atypical depression as a subtype that is preferentially responsive to monoamine oxidase inhibitors is supported.