Are all antidepressants alike?

Antidepressants are indicated in about 40 different disorders, including mood disorders, anxiety disorders, and other disorders. We propose to call these disorders antidepressani-responsive disorders (ARDs). We describe the clinical and biological criteria that differentiate the antidepressants. Although antidepressants share the same clinical efficacy in most ARDs, the configuration of adverse drug reactions varies widely. The recent antidepressants should be preferred to the tricyclic antidepressants as first-line treatment because of their lesser risk of severe adverse drug reactions. However, several recent antidepressants have been associated with severe complications such as the serotonin syndrome and the withdrawal syndrome. Patient characteristics should be included as a criterion to predict both unwanted and favorable effects.     

Issues & opinions: Are fibrillation potentials and positive sharp waves the same? No

Electrodiagnostic medicine consultants report electrical activity in muscle recorded at rest and during voluntary movement by means of waveform and firing rate characteristics. This principle allows us to distinguish fibrillation potentials from positive sharp waves. Although in most cases these two potentials have the same clinical significance, there are at least five different situations in which they do not have an identical meaning: (1) positive sharp waves can be recorded earlier after a peripheral nerve injury than can fibrillation potentials; (2) occasionally, nonclinically significant diffuse positive sharp wave activity may be seen in the absence of fibrillation activity (i.e., “EMG disease”); (3) positive sharp waves may be seen in distal muscles of “normal” subjects without the presence of fibrillation activity or clinical significance; (4) positive sharp waves without fibrillation potentials may be seen following local muscle trauma; and (5) positive sharp waves may be seen alone in some demyelinating polyneuropathies. By accurately describing the observed potentials, the electrodiagnostic medicine consultant may be able to obtain more clinically useful information from an electrodiagnostic study. © 1996 John Wiley & Sons, Inc.     

Are gender differences important for the clinical effects of antidepressants?

OBJECTIVE: Gender differences in antidepressant treatment response, side effects, dropout rates, and plasma concentrations were examined in patients with major and predominantly melancholic depression. METHOD: The study included a subgroup of 292 inpatients (96 men, 196 women) from three Danish double-blind, randomized, controlled trials. All patients completed a 5-week treatment period and fulfilled the DSM-III or DSM-III-R criteria for major depression. Clomipramine (150 mg/day) was the reference treatment, and comparable treatments were citalopram (40 mg/day), paroxetine (30 mg/day), and moclobemide (400 mg/day). Assessments were performed by using the 17-item Hamilton Depression Rating Scale and the Udvalg for Kliniske Unders?gelser Side Effect Rating Scale. In a subgroup of 110 patients, weekly measurements of clomipramine plasma concentrations were obtained. Nonparametric statistical tests and multiple linear and logistic regression models were used for statistical evaluations. RESULTS: Both genders had similar remission rates (Hamilton depression scale score <8) when treated with clomipramine and had significantly higher remission rates with clomipramine than with the comparable treatments. The plasma concentrations of clomipramine were significantly higher for female than for male patients. No gender differences were found in posttreatment Hamilton depression scale scores, nor did the therapeutic effects of treatment depend on gender. Rates of dropout and side effects were similar for men and women. No relationship between plasma concentrations, gender, and therapeutic outcome was found. CONCLUSIONS: In a group of patients with major and predominantly melancholic depression, differentiation according to gender was not important in treatment with common antidepressants. Women appeared to have higher plasma concentrations of tricyclic antidepressants than men. The consequences of this difference for clinical effects are unclear. Gender-specific recommendations for dosing of tricyclic antidepressants may be considered.     

Psychopharmacology of anticonvulsants: do all anticonvulsants have the same mechanism of action?

ISSUE: Anticonvulsants are not a single therapeutic class, but are composed of multiple distinct subclasses with different mechanisms of action, efficacies, and side effects.     

Are psychiatrists affecting the legal process by answering legal questions?

BACKGROUND: Psychiatrists are often asked to answer legal questions. The extent to which they answer strictly legal rather than medical matters is not known. AIM: To investigate how strongly psychiatrists in England and Wales express opinions on one legal question - that of diminished responsibility in respect of a murder charge, and how this is related to outcome in court. METHOD Our data were extracted from psychiatric reports and case files supplied by the then Department of Constitutional Affairs (now the Ministry of Justice) on cases heard in the Crown Courts between 1 January 1997 and 31 December 2001 in which the defence of diminished responsibility had been raised. The cases had been selected by the Law Commission in their earlier review of partial defences to murder. We devised a reliable system of rating the presence/absence and strength of expression of a legal opinion in the medical reports. We tested the data for relationship between nature and strength of opinion and progression to trial and verdict. RESULTS Psychiatric reports were available on 143 of 156 cases in which diminished responsibility was considered. They yielded 338 opinions on at least one aspect of diminished responsibility. In 110 (93%) of the 118 cases in which there was a diminished verdict, this was made without trial and, therefore, without reference to a jury. In only eight (27%) out of the 30 cases that went to trial, was a diminished responsibility verdict made. Half of the reports (169) gave a clear opinion on diminished responsibility, a third (121) invited the court to draw a particular conclusion and only 11% (36) provided relevant evidence without answering the legal questions. When there was an opinion or an invitation to make a finding on the legal question, a trial was less likely. A trial was also less likely if reports agreed on what the verdict should be. CONCLUSIONS Psychiatrists frequently answer the legal question of diminished responsibility. The judiciary and medical experts should join in research to examine the consequences of different styles or approaches in presentation of essentially similar evidence in court.     

For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same?

Low-molecular-weight heparin compounds have been used in the treatment of patients with venous thromboembolism for approximately 15 years. Ever since their introduction, there has been discussion about whether low-molecular-weight heparin compounds differ in their efficacy and safety. The best answer would be provided by direct comparison of different low-molecular-weight heparin preparations; however, these trials have not been conducted. Classical meta-analysis has its limitations for such a comparison since only a very small number of trials with the respective low-molecular-weight heparin compounds are available. The objective of the present analysis has been the use of meta-regression to compare the efficacy and safety of different low-molecular-weight heparin compounds in the initial treatment of patients with venous thromboembolism. We used computerized literature searches to identify studies that compared dose-adjusted unfractionated heparin treatment with fixed dose subcutaneous low-molecular-weight heparin treatment in patients with established venous thromboembolism. The individual odds ratios of the studies were plotted against the absolute percentage of the major outcomes in the unfractionated heparin control group. Linear regression was used to find differences between different low-molecular-weight heparin compounds. There appears to be some variation in efficacy and safety among the currently available low-molecular-weight heparin preparations.     

Are antidepressants effective in the acute and long-term treatment of depression? Sic et Non

The efficacy of antidepressant treatment of major depression remains a matter of controversy. A review of acute treatment studies suggests that for relatively more severe episodes of major depression, antidepressants are superior to treatment in the "placebo group;" however, there are numerous methodological confounds in the available literature. (Some recent, preliminary evidence suggests that antidepressants may also be of benefit in some less severely depressed populations).There is moderately strong evidence that, compared with placebo, maintenance antidepressant treatment reduces six-month relapse rates in major depression; however, it is less clear that antidepressants prevent actual recurrence of depression in the longer term. There is evidence of both over-use and under-use of antidepressant treatment, and there appears to be a "mismatch" between diagnosis and optimal treatment of depression in some clinical settings. Better designed studies are needed to resolve these uncertainties and to investigate such putative conditions as "oppositional tolerance" to long-term antidepressant treatment. The author advocates a conservative approach to antidepressant treatment, as well as a substantially extended "tapering" period when antidepressants are discontinued.     

Are we all the same? The critical role of translational brain,behavior, and immunity research in East Asia

Traditional Chinese medicine (TCM) is founded on the idea that the “Mind and Body” are all interconnected. When you have a difficult time or disturbing lifestyle and experience a series of somatic and psychological symptoms mimicking inflammation-induced sickness behaviors, the TCM practitioners would be very likely to give you a diagnosis of “On Fire” and prescribe specific food intervention and herbal medicine, which might be considered anti-inflammatory to “cool you down.” Psychoneuroimmunology has been long stemmed in ancient medicine.     

Are antidepressants carcinogenic? A review of preclinical and clinical studies

BACKGROUND: Antidepressants are widely prescribed for mood and anxiety disorders, though reports in the oncology and epidemiology literature have suggested these agents may possess tumor initiating and/or promoting properties, raising questions about safe long-term use in patients. The author conducted a review of the preclinical and clinical literature on the connection between antidepressants and carcinogenesis. METHOD: A MEDLINE search was conducted for English-language articles published from 1966 to 2002 using the search terms antidepressants, tumors, carcinogenesis, and cancer, as well as specific antidepressant names. Additional studies were ascertained through cross-references. RESULTS: Preclinical studies found evidence for both tumor promotion and suppression, though the majority of studies predominantly examined tricyclic antidepressants (TCAs), with 1 report suggesting that TCAs with a nitrogen atom in the central ring are genotoxic. Of 13 clinical studies, 3 found a significant increase, 4 noted a trend increase, and 6 found no increase in risk for cancer with antidepressant (mostly TCA) use. Methodologic differences could account for some of the discrepancies found in the clinical studies, while questions about the validity for humans of the preclinical models raise doubt about the significance of those findings. CONCLUSION: While there is some suggestive evidence of an association between antidepressant use and cancer, the link is, at this time, questionable but deserving of further study, especially with newer agents. Clinicians should not withhold antidepressant medication when indicated, as the risks of untreated depressive and anxiety disorders exceed the as yet unsubstantiated risk of tumor formation in such patients.     

Are the effects of the antidepressants amitriptyline, maprotiline, and fluoxetine on inhibitory avoidance state-dependent?

State-dependent learning (SDL) is a phenomenon in which the retrieval of newly acquired information is possible if the subject is in the same physiological state as during the encoding phase. SDL makes it possible to separate the effects of drugs per se on learning from the effects due to changes in drug state during the task. The present work was designed to investigate whether the antidepressants amitriptyline (30 mg/kg), maprotiline (25 mg/kg), and fluoxetine (15 mg/kg) produce SDL of the inhibitory avoidance conditioning in male and female CD1 mice. In three separate experiments, independent groups were used for each pharmacological treatment and for each sex using a 2 x 2 experimental design. The results do not show SDL in any of the drugs. In the case of amitriptilyline, the data can be attributed to a memorization deficit, while the maprotiline results are interpreted as simultaneously influenced by memorization deficit and performance facilitation due to motor impairment. Fluoxetine treatment did not produce any deteriorating effect on the conditioning. Drugs had some different effects on the performance of males and females, males showing a slightly higher deterioration than females with administration of amitriptyline and maprotiline. This study shows that these antidepressants affect the acquisition/consolidation but not the retrieval process in the inhibitory avoidance learning.     

Is paranoid schizophrenia the most common subtype? Comparison of subtype diagnoses by Japanese and European psychiatrists, using the summaries of the same patients

We compared the subtype diagnoses of schizophrenia (ICD-10) of 58 Japanese and 61 European psychiatrists matched for clinical experience using 10 case summaries. As a result, there are marked differences between Japanese and European psychiatrists in the mode of subtype diagnoses of schizophrenia rather than in the clinical pictures of the patients themselves; the hebephrenic type (F20.1) was more likely to be diagnosed by Japanese psychiatrists, while the paranoid type (F20.0) was more frequently diagnosed by European psychiatrists. Japanese psychiatrists take into account the patient's age at onset and the clinical course of the disease in identifying the subtype, while European psychiatrists tend to focus on the presenting symptoms, particularly paranoid symptoms.     

Are semantic and syntactic cues inducing the same processes in the identification of word order?

The purpose of this study was to find a common pattern of event-related potential (ERP) fluctuations regardless of the type of information (either semantic or syntactic) determining the presence of a reversed word order. ERPs were recorded while subjects read Spanish transitive sentences in which either semantic or syntactic information determined the actual word order. On the one hand (semantic condition), the order could be reversed by using an inanimate noun in the first noun phrase (NP), together with a verb representing an action that cannot correspond to an inanimate entity. On the other hand (syntactic condition), word order could be manipulated depending on the presence of a preposition preceding the second NP, which confirms the preferred word order, or a determiner, conveying a reversed word order. Interestingly, the inanimate first noun elicited a frontal negativity, which could be interpreted as the detection of an initial difficulty for using that noun as the subject of the sentence. At the point of disambiguation in either condition, a late posterior positivity was observed. The P600/SPS might, therefore, be an indicator of the syntactic processing costs incurred by the variation of word order, reflecting phrase structure reallocation processes common to this operation regardless of the cue used.