Open-label sildenafil treatment of partial and non-responders to double-blind treatment in men with antidepressant-associated sexual dysfunction.

Fifty partial and non-responders (Clinical Global Impression-Sexual Function (CGI-SF) score>2), out of 76 men who completed a 6-week, double-blind, placebo-controlled trial of sildenafil treatment for serotonergic antidepressant-associated sexual dysfunction, were eligible for an additional 6-week trial of open-label sildenafil (50 mg adjustable to 100 mg) under the same protocol, with blind maintained to initial assignment. Participation (double-blind and open-label) required major depressive disorder in remission (MDD-R) and continuing antidepressant medication. Forty-three entered open-label study: 16/17 initially randomized to sildenafil (sildenafil/sildenafil) and 27/33 initially randomized to placebo (placebo/sildenafil). Thirty-five of 43 (81%) achieved full response (CGI-SF

Consideration of the relevance of ethological animal models for human repetitive behavioral spectrum disorders.

Treatment successes of various stereotyped behaviors in animals and humans has renewed interest in ethologic animal models for the study of psychiatric disorders. This report presents another such behavior occurring in horses to weaving. This anomalous, repetitive, and purposeless behavior draws analogies to human compulsive spectrum behaviors. A "weaver" provided an opportunity to evaluate serotonin, dopamine, and opioid neurotransmitter system contributions by probing each with a selective agent in A-B-A-C-A-D design. The horse was treated in sequential 1-month periods separated by 1-month washouts with a serotonin transport inhibitor (SRI), opiate antagonist (OA), and neuroleptic (DA). Videotape was taken weekly and analyzed by two blind raters. Frequency of head swings, latency to onset, and severity were recorded. The SRI showed > 95% symptom reduction, the DA 40%, and OA 30%. The findings suggest that neurochemical explanations of disturbance based on single drug vs. placebo trials may be oversimplified. Multiple-system probes are needed to dissect complex interactive biological systems. Animal model research can have an important role in such investigations.

Spontaneous remission of MAOI-induced anorgasmia.

The authors present three case reports illustrating that a conservative approach to anorgasmia induced by effective treatment with the monoamine oxidase inhibitor (MAOI) phenelzine can result in spontaneous remission. Precipitously stopping phenelzine or adding another medication to counteract the side effect can be avoided. The apparent synchrony between the development of the side effect of anorgasmia and positive treatment response may represent a valuable clinical marker.

Response of panic disorder and resistance of depression to imipramine.

The authors present the cases of two patients with panic disorder and major depression whose panic responded to imipramine but whose depression did not.

Evaluation of diagnostic criteria for borderline personality disorder.

A comparison of 17 narrowly defined borderline patients with 20 nonpatient control subjects indicated that certain individual and combinations of criteria may be more highly correlated with the disorder than others. Requiring any four or certain specific combinations of two or three of the five most discriminating criteria provided the optimal balance of sensitivity, specificity, predictive power, and diagnostic efficiency considerations. Fewer than five DSM-III-R criteria adequately identified the patients.

Psychopathology complicating acquired immune deficiency syndrome (AIDS).

The authors report the case of a man with acquired immune deficiency syndrome (AIDS) who was admitted to the hospital because of an organic mental syndrome with affective and delusional features.

Effect of hospital admission on DST results.

The authors examined the dexamethasone suppression test (DST) responses of 41 patients with primary major depressive disorder and 40 patients with other psychiatric disorders who were tested within 2-6 days of hospital admission. Significantly more patients with primary depression who were tested on day 2 demonstrated abnormal cortisol suppression than those who were tested on days 3, 4, or 3-6 and than patients with other psychiatric disorders regardless of test day. These results suggest that patients with primary depression may be sensitive to psychophysiologic stresses associated with hospital admission and that the utility of the DST may require further evaluation vis-à-vis the day of DST administration.

The comorbidity of borderline personality disorder and other DSM-III-R axis II personality disorders.

OBJECTIVE: This study examines the comorbidity of DSM-III-R borderline personality disorder and the other axis II personality disorders. The extent and direction of overlap provides a measure of the clarity of its diagnostic boundaries and descriptive validity. METHOD: In 110 outpatients without concurrent major axis I conditions, axis II diagnoses were assessed in semistructured format and all DSM-III-R personality disorder criteria were rated. Multiple diagnoses were recorded. RESULTS: Twenty-two patients (20%) met criteria for borderline personality disorder; 18 (82%) had at least one additional personality disorder diagnosis. Using measures of frequencies and intercorrelation coefficients, the authors found that overlap was extensive and not confined to any one of the three designated axis II clusters. Factor analysis revealed 1) a group containing borderline personality disorder with paranoid, histrionic, narcissistic, antisocial, and passive-aggressive personality disorders and 2) another grouping of schizoid, schizotypal, avoidant, obsessive-compulsive, and self-defeating personality disorders. CONCLUSIONS: Borderline personality disorder appears to constitute a broad, heterogeneous category with unclear boundaries that embraces a general personality disorder concept. Both further refinement of the borderline personality disorder construct and investigation into alternative models to the DSM-III-R axis II classification system are suggested.

Efficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors.

OBJECTIVE: This study was an evaluation of whether sildenafil citrate is effective for the treatment of erectile dysfunction in men taking concomitant serotonin-reuptake-inhibiting antidepressants. METHOD: A retrospective subanalysis of combined data from 10 phase II/III double-blind, placebo-controlled, fixed- and flexible-dose trials (12-26 weeks) identified a group of men with erectile dysfunction receiving 5 to 200 mg/day of sildenafil (N=65) or placebo (N=33) and concomitant serotonin-reuptake-inhibiting antidepressants. Efficacy was measured by responses to questions from the International Index of Erectile Function on ability to achieve erection, ability to maintain erection, ejaculation frequency, orgasm frequency, and sexual desire. RESULTS: Patients with erectile dysfunction receiving sildenafil and concomitant serotonergic antidepressants had significantly greater improvements in ability to achieve and maintain an erection, frequency of ejaculation, and orgasm frequency than did patients receiving placebo, without increased sexual desire. CONCLUSIONS: Sildenafil significantly improved erectile dysfunction in patients taking concomitant serotonergic antidepressants.

Urinary incontinence in patients receiving neuroleptics.

This paper presents a series of case reports making the observation of a possible association between neuroleptic drug therapy and urinary incontinence. The incontinence was limited and not of the overflow or stress variety. Anticholinergic compounds or drug action did not seem to influence or account for the findings. A central basis is postulated for consideration and warrants further study.

Carbamazepine in bipolar-depressed disorder complicated by tricyclic antidepressant switching: case report.

The use of carbamazepine in a depressed bipolar patient with a history of manic switching with tricyclic antidepressants is described. Carbamazepine effectively treated the depression and mania was avoided.

Antidepressant medication change in a clinical treatment setting: a comparison of the effectiveness of selective serotonin reuptake inhibitors.

BACKGROUND: This investigation focuses on the 3 most frequently used selective serotonin reuptake inhibitors (SSRIs) (paroxetine, fluoxetine, sertraline) and examines the rate of medication switches as a measure of effectiveness. We answer 2 questions: (1) What is the likelihood that a patient starting treatment with an SSRI will complete treatment with the same agent? and (2) Depending on the initial SSRI agent used, do patients switch at different frequencies? METHOD: A retrospective chart review was performed on 2779 patients treated in a university outpatient clinic from March 1995 to January 1997. Of these, 263 patients given antidepressants were randomly selected: 214 were prescribed SSRIs; 24, novel antidepressants; and 25, tricyclic antidepressants. RESULTS: There was no significant difference in rate of switching between the different classes of antidepressant (p = .1) nor between drugs within the SSRI class (p = .513). When medication change was the independent factor, significant differences between the groups were total time in treatment and number of visits (p < .001 and p = .011, respectively). Age, education, and Clinical Global Impressions-Severity of Illness scale scores (admission, discharge, and change) were not significantly different between the groups. CONCLUSION: Approximately 25% of patients started with an SSRI will switch to another antidepressant in the course of their treatment. The SSRIs appear to be equivalent in effectiveness. They are not interchangeable, because patients who discontinue one SSRI for lack of tolerability or response can generally be treated effectively with another.

Clinical utilization of the dexamethasone suppression test.

To explore the procedural nature and clinical impact of the dexamethasone suppression test (DST) in psychiatric hospital practice, case records of 115 consecutive psychiatric inpatients who had undergone overnight DSTs were examined. It was found that clinicians often fail to perform the test according to previously established guidelines and that the results obtained rarely affect clinical psychiatric management in a positive manner.

Sildenafil for iatrogenic serotonergic antidepressant medication-induced sexual dysfunction in 4 patients.

OBJECTIVE: To evaluate the effect of sildenafil on iatrogenic serotonergic antidepressant-induced sexual dysfunction. METHOD: Four outpatients (2 men, 2 women) who developed sexual dysfunction (erectile impotence, anorgasmia) during treatment with a serotonin reuptake inhibitor antidepressant for psychiatric disorder were selected. Each subject was initially prescribed sildenafil 50 mg to be taken approximately 1 hour before sexual activity. The dose was increased to 100 mg for a partial or failed response. RESULTS: Four cases are detailed in case report fashion. All 4 had rapid reversal of their sexual dysfunction, usually with the first dose. Reversal equates to 1 successful use of sildenafil in each of 2 patients and 3 uses in 2 patients. CONCLUSION: Sildenafil may be an effective treatment for serotonergic antidepressant-induced sexual dysfunction and deserves further evaluation in randomized placebo-controlled studies.

Effects of trifluoperazine, chlorpromazine, and haloperidol upon temporal information processing by schizophrenic patients.

Healthy controls, unmedicated, actively symptomatic schizophrenics, and similar patients undergoing treatment with either trifluoperazine, chlorpromazine, or haloperidol were studied with tests of temporal discrimination and measures of transmitted information shown previously to be sensitive to various kinds of brain dysfunction, including haloperidol effects in a nonpsychotic population. Variations in psychophysical method, cognitive load, discrimination complexity, and sense-mode conditions permitted representative sampling of the temporal processing. Untreated, actively psychotic patients showed no impairment of temporal processing while all three antipsychotic medications were associated with significant deficit; trifluoperazine and haloperidol produced the most deficit, with chlorpromazine in the middle between the higher potency drugs on the one hand and unmedicated patients and healthy controls on the other.

The dexamethasone suppression test in depressive, non-depressive and schizoaffective psychosis.

The authors examined the 24-h plasma cortisol response to dexamethasone in 19 patients with co-existing depressive and psychotic features and in 12 non-depressed patients with only psychotic features. The rate and degree of abnormal dexamethasone suppression was greatest in patients who met RDC criteria for primary depressive disorder. Patients who met criteria for schizoaffective--mainly schizophrenic--depressed and other psychotic disorders did not differ from each other in their response to dexamethasone. These data suggest that the DST may have utility in the diagnostic evaluation of some patients with depressive and psychotic features.

An overview of somatic treatment of psychosis during pregnancy and postpartum.

Treatment and management of the psychotic pregnant patient is insufficiently covered by most standard texts and the current literature. To date, there are no controlled studies on the efficacy of different therapeutic modalities during pregnancy. Medications that have proved effective in the treatment of the various psychoses are not without added risk for the pregnant patient. However, there is no effective medical treatment without attendant risk. Although the psychotic pregnant patient presents a therapeutic dilemma, these patients can be effectively treated by a program that allows for flexibility and innovation within the framework of sound conservative medical practice. Professional territorial difficulties can be avoided by a unified effort.

Formulary restriction of selective serotonin reuptake inhibitors for depression: potential pitfalls.

The American healthcare market is currently estimated at more than 900 billion US dollars with double digit rising costs per year. Psychotropic agent costs have more than kept pace with market increases. Medication acquisition costs are an obvious focus for limiting costs in various care systems. Restrictive formularies are a common method of attempting to limit costs. To support our opinion that a single agent is ill advised, we explored the available evidence on the intended and unintended consequences of having a single or exclusive selective serotonin reuptake inhibitor (SSRI) on a formulary. Central to this position is an assumption of the interchangeability of SSRIs; we examined the evidence for and against this through a model to determine the probability of interchangeability. We conclude that the practice of having a single SSRI on the formulary for a healthcare plan seems ill founded. Patients who switch antidepressants remain in treatment 50% longer and cost approximately 50% more to treat in a more costly treatment setting. Giving the primary care physician several antidepressant choices can provide more options to continue treatment of his or her patient in the less expensive primary care setting. In terms of cost containment, formulary restrictions are far more likely to have the opposite effect.

Theoretical and methodological issues in psychiatric comorbidity.

The occurrence of multiple diagnoses in one patient is a phenomenon of major clinical and theoretical importance. This paper reviews the various factors involved in real and artifactual comorbidity. Important causes of spurious comorbidity are discussed, including invalidity of the individual diagnoses, use of inappropriate diagnostic paradigms, descriptive overlap of diagnostic criteria, ascertainment bias, and diagnostic bias. To illustrate some of the concepts discussed, two examples are presented: the comorbidity of schizophrenia and substance use disorders, and the comorbidity of posttraumatic stress disorder and major depression. The study of comorbidity can advance psychiatry by helping us to clarify our thinking about categories of illness and the boundaries between them, as well as the relationships among these categories.

Modeling the pharmacoeconomic cost of three selective serotonin reuptake inhibitors.

The authors present a method for modeling cost data on three selective serotonin reuptake inhibitors (SSRIs)-fluoxetine, paroxetine, and sertraline-from a large clinical outcomes study in a university-affiliated mental health center. Using data from 2,779 patients, average drug cost per day was calculated based on the percentage of patients on each daily dose of each medication. Given no overall significant difference between the SSRIs in effectiveness, the actual average cost per day determined by dose distribution was $1.79 for fluoxetine, $1.41 for paroxetine, and $1.21 for sertraline (using halved 100 mg tablets). The results suggest that cost can serve as one measure to help guide choice of medications.