Stimulus intensity in transcranial magnetic stimulation (TMS) studies.
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Depressive Disorder↗
Biomedical subjects
P B Mitchell
Publications and source records attributed to P B Mitchell.
Indicators of suicide over 10 years in a specialist mood disorders unit sample.
BACKGROUND: There are few firm data to guide the clinician in identifying individual depressed patients who may be at high risk for completing suicide. In particular, there have been few prospective studies of well-characterized depressed patients to determine indicators of such future events. METHOD: Eight hundred thirteen patients with a major depressive episode (DSM-III, DSM-III-R, or DSM-IV criteria) were assessed in detail in a specialist Mood Disorders Unit (MDU) over a 10-year period. Follow-up at the end of that period (mean = 5.1 years) confirmed that 31 patients (3.8%) had completed suicide. The suicide completers were compared on a broad range of clinical and demographic variables obtained at baseline with (1) the total remaining depressed sample, (2) 31 age- and sex-matched subjects who were confirmed to be alive and had never attempted suicide, and (3) 24 age- and sex-matched living subjects who had made at least 1 suicide attempt. RESULTS: The most consistent finding, across all 3 comparisons, was that the suicide completers were more likely to have been inpatients at the time of the index MDU assessment. Other characteristics of completers were a greater number of prior admissions for depression, being older and in a relationship, and being male and married or female and single. Somewhat paradoxically, suicide completers also evidenced fewer previous suicide attempts and less suicidal ideation compared with living subjects who had attempted suicide at the time of index assessment. CONCLUSION: Overall, we were able to find few predictors of later suicide in this sample. Those who completed suicide demonstrated evidence of more severe illness over a lifetime (for example, having more admissions). but revealed less suicidal ideation at the time of the index MDU assessment. While these features were statistically significant, they are of limited usefulness in predicting suicide in an individual patient.
Adult↗
Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation.
BACKGROUND: There is preliminary evidence that repetitive transcranial magnetic stimulation (rTMS) may be useful for the treatment of obsessive-compulsive disorder (OCD), but no definitive study has been published, and the effect of laterality of stimulation is uncertain. METHOD: Subjects (N = 12) with resistant OCD were allocated randomly to either right or left prefrontal rTMS daily for 2 weeks and were assessed by an independent rater at 1 and 2 weeks and 1 month later. RESULTS: Subjects had an overall significant improvement in the obsessions (p < .01), compulsions (p < .01), and total (p < .01) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) after 2 weeks and at 1-month follow-up. This improvement was significant for obsessions (p < .05) and tended to significance for total Y-BOCS scores (p = .06) after correction for changes in depression scores on the Montgomery-Asberg Depression Rating Scale. There was no significant difference between right- and left-sided rTMS on any of the parameters examined. Two subjects (33%) in each group showed a clinically significant improvement that persisted at I month but with relapse later in I subject. CONCLUSION: A proportion (about one quarter) of patients with resistant OCD appear to respond to rTMS to either prefrontal lobe, although in the absence of a sham treatment group in this study, we cannot rule out the possibility of this being a placebo response. This treatment warrants further investigation to better establish its efficacy and examine the best parameters for response.
Adult↗
The clinical features of bipolar depression: a comparison with matched major depressive disorder patients.
BACKGROUND: Despite a resurgence of interest in the treatment of bipolar depression, there have been few controlled studies of the clinical characteristics of this condition. Identification of any distinctive clinical "signatures" of bipolar depression would be helpful in determining treatment options in the clinical setting. METHOD: From a cohort of 270 inpatients and outpatients assessed in detail during a DSM-IV major depressive episode, 39 bipolar I disorder patients were identified and closely matched with 39 major depressive disorder patients for gender, age, and the presence or absence of DSM-IV melancholic subtype. Patients were compared on a broad range of parameters including the Hamilton Rating Scale for Depression (depression severity), 54 depressive symptoms, the Newcastle Endogenous Depression Diagnostic Index, 3 family history items, 2 physical health items, the CORE scale (psychomotor disturbance), and 5 history items. RESULTS: Although the bipolar patients were no more severely depressed than the major depressive disorder controls, they were more likely to demonstrate psychomotor-retarded melancholic and atypical depressive features and to have had previous episodes of psychotic depression. These findings were largely duplicated even when the population was confined to those with DSM-IV melancholia. CONCLUSION: The clinical admixture of psychomotor-retarded melancholic signs and symptoms, "atypical" features, and (less frequently) psychosis may provide a "bipolar signature" in clinical scenarios when there is uncertainty concerning the polarity of a depressive presentation.
Adult↗
Recent trends in the use of antidepressant drugs in Australia, 1990-1998.
OBJECTIVE: To determine the pattern of use of antidepressant drugs in the Australian community, 1990-1998, and to compare this with those of other developed countries. DESIGN: Retrospective analyses of prescription and sales data, together with information about patient encounters for depression (from an ongoing survey of service provision by general practitioners) and population-based prevalence estimates for affective disorders (from community health surveys). MAIN OUTCOME MEASURES: National and international consumption of antidepressants, expressed in defined daily doses (DDDs) per 1000 population per day. Changes in both the frequency of general practice patient encounters for depression and population-based prevalence estimates for affective disorders. RESULTS: Dispensing of antidepressant prescriptions through community pharmacies in Australia increased from an estimated 12.4 DDDs/1000 population per day in 1990 (5.1 million prescriptions) to 35.7 DDDs/1000 population/day in 1998 (8.2 million prescriptions). There has been a rapid market uptake of the selective serotonin reuptake inhibitors (SSRIs), accompanied by a decrease of only 25% in the use of tricyclic antidepressants (TCAs). In 1998, the level of antidepressant use in Australia was similar to that of the United States, while the rate of increase in use between 1993 and 1998 was second only to that of Sweden. In Australia, depression has risen from the tenth most common problem managed in general practice in 1990-91 to the fourth in 1998-99, and the number of people reporting depression in the National Health Surveys (1995 v 1989-90) has almost doubled. Of the prescriptions dispensed in 1998 for antidepressant drugs subsidised by the Pharmaceutical Benefits Scheme, 85% were written by general practitioners, and 11.2% by psychiatrists. CONCLUSIONS: As in most developed countries, antidepressant use increased between 1990 and 1998. The rapid market uptake of the new antidepressants, particularly SSRIs, is likely to have been driven by increased awareness of depression, together with availability and promotion of new therapies.
Antidepressive Agents↗
Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some "sham" forms active?
BACKGROUND: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. METHODS: In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. RESULTS: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. CONCLUSIONS: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.
Adult↗
Therapeutic drug monitoring of psychotropic medications.
Therapeutic drug monitoring (TDM) of a number of psychotropic medications has proven to be of value, enabling minimization of the limitations of considerable genetic variability in their metabolism and the high rates of poor compliance with many psychiatric disorders. Therapeutic ranges have been established for lithium, some of the tricyclic antidepressants, and clozapine. TDM has also been shown to be useful in avoiding toxicity (as many psychotropics have narrow therapeutic indices), particularly that due to interactions with other compounds.
Humans↗
Efficacy of venlafaxine and predictors of response in a prospective open-label study of patients with treatment-resistant major depression.
The aim of this study was to replicate the findings of a 1994 study, in which a 30% response rate to venlafaxine was found in patients with treatment-refractory depression, as well as to examine for any predictors of such an outcome. The study was an 8-week, open-label, prospective investigation of venlafaxine in doses up to 300 mg in 312 patients fulfilling criteria for either "absolute" or "relative" treatment resistance. By week 8, 52.6% of the patients had responded, which was defined as a 50% reduction in scores on the Montgomery-Asberg Depression Rating Scale; 49% of those defined with "absolute resistance" demonstrated such an outcome. Forty-five percent of the patients with absolute resistance who had failed to respond to at least one tricyclic antidepressant responded to venlafaxine. Response rates were higher in those with an absence (57.5%) compared with the presence (31.0%) of any comorbid psychiatric disorder (p < 0.001), "marked" (60.3%) compared with "mild or moderate" (51.6%) or "severe" (43.4%) baseline ratings on the patient-rated Clinical Global Impressions Scale (p < 0.05), and "relative" (61%) compared with "absolute" resistance (49%) (p = 0.06). Furthermore, improvement in scores of 20% or 30% at weeks 1 or 2 was associated with higher rates of final response (p < 0.0005). After logistic regression, both comorbid psychiatric illness (p < 0.001) and early improvement (p < 0.0001) remained significant and independent predictors of final response.
Adult↗
Lithium treatment for bipolar disorder.
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Australia↗
John Cade and Frank Macfarlane Burnet anniversaries.
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Australia↗
John Cade and the discovery of lithium treatment for manic depressive illness.
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Australia↗
Nonparametric simulation-based statistical analyses for bipolar affective disorder locus on chromosome 21q22.3.
Straub et al. [1994: Nat Genet 8:291-296] reported a candidate bipolar affective disorder (BAD) locus on chromosome 21q22.3. As a replication study, we analyzed 12 Australian BAD pedigrees for the presence of excess allele sharing and cosegregation with the putative chromosome 21q22.3 BAD locus, using six microsatellite markers. The nonparametric simulation-based statistic SimAPM produced positive results for the marker PFKL (P < 0.001) and D21S198 (P = 0.007). PFKL also demonstrated linkage (P < 0.001) when analyzed using the more conservative statistic, SimIBD. Comparable results were obtained when using the original APM statistic (P = 0.02 for D21S198). However, other nonparametric analyses such as GENEHUNTER and model-free linkage (MFLINK) analysis did not yield significant results. Combined LOD scores for the 12 families were strongly negative for all six markers under six genetic models. Two-point and multipoint analyses of individual families revealed one family, family 17, with maximal LOD scores greater than 1.41 for the 10.5-cM region between PFKL and D21S198. This report provides additional support for the suggestive linkage of a susceptibility locus for BAD on chromosome 21q22.3.
Bipolar Disorder↗
On the 50th anniversary of John Cade's discovery of the anti-manic effect of lithium.
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Antimanic Agents↗
The place of anticonvulsants and other putative mood stabilisers in the treatment of bipolar disorder.
While lithium is an effective mood stabiliser still in widespread clinical use, a significant proportion of patients either respond poorly or are unable to tolerate its adverse effects. In the 1960s and 1970s preliminary reports of the possible effectiveness of carbamazepine and valproate began to appear, with confirmatory controlled studies being undertaken in the 1980s and 1990s. In recent years, further putative mood-stabilising agents have been described, in particular some of the newer anticonvulsants and the atypical antipsychotics. This paper critically evaluates the current evidential basis for claims for the efficacy of these compounds in bipolar disorder.
Affect↗
Practitioner review: electroconvulsive therapy in adolescents.
There is increasing interest regarding electroconvulsive therapy (ECT) in young persons but limited information about its optimal use. This paper reviews the indications, effectiveness, and side effects of the treatment in the teenage population and their implications for everyday clinical practice. There is particular reference to factors influencing the clinician to recommend or advise against convulsive therapy, steps in the assessment of patients, and consent issues. Practical aspects of ECT administration are also examined, including treatment locale, anaesthesia, electrode position, stimulus characteristics, EEG monitoring, and use of psychotropics during and after the ECT course.
Adolescent↗
Psychotropic medications in pregnant women: treatment dilemmas.
OBJECTIVES: To review the evidence from all studies of adverse effects on infant outcome of psychotropic medications taken during pregnancy. DATA SOURCES: MEDLINE January 1976-February 1998, EMBASE 1976-February 1998, and bibliographies of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: All studies focusing on adverse effects associated with psychotropic drug use during pregnancy, with a particular focus on prospective controlled studies. OUTCOME CRITERIA: Congenital anomalies, perinatal complications and neurobehavioural sequelae. DATA SYNTHESIS: 23 studies were identified, nine of which were prospective controlled studies: five involving antidepressants (tricyclic antidepressants [TCAs] and selective serotonin reuptake inhibitors [SSRIs]), one each involving lithium and carbamazepine, and two involving benzodiazepines. As statistical synthesis was not possible given the heterogeneity of outcome criteria, a qualitative review is provided. Neither the SSRIs nor the TCAs appear to cause major congenital anomalies, but both may be associated with a small increased risk of minor anomalies, prematurity and neonatal complications. Benzodiazepines, lithium, anticonvulsants and chlorpromazine do lead to an increased rate of congenital anomalies as well as neonatal problems. Studies of longer-term neurobehavioural sequelae of psychotropic medications are very limited, but at present do not indicate any adverse effects. CONCLUSIONS: While some psychotropes are associated with congenital anomalies and perinatal complications, mental illness per se may also be associated with an adverse outcome in the infant. Clearly, the risks to both mother and infant need to be carefully weighed and discussed with the parents.
Anti-Anxiety Agents↗
A susceptibility locus for bipolar affective disorder on chromosome 4q35.
Bipolar affective disorder (BAD) affects approximately 1% of the population and shows strong heritability. To identify potential BAD susceptibility loci, we undertook a 15-cM genome screen, using 214 microsatellite markers on the 35 most informative individuals of a large, statistically powerful pedigree. Data were analyzed by parametric two-point linkage methods under several diagnostic models. LOD scores >1.00 were obtained for 21 markers, with four of these >2.00 for at least one model. The remaining 52 individuals in the family were genotyped with these four markers, and LOD scores remained positive for three markers. A more intensive screen was undertaken in these regions, with the most positive results being obtained for chromosome 4q35. Using a dominant model of inheritance with 90% maximum age-specific penetrance and including bipolar I, II, schizoaffective/mania, and unipolar individuals as affected, we obtained a maximum two-point LOD score of 2.20 (theta = .15) at D4S1652 and a maximum three-point LOD score of 3.19 between D4S408 and D4S2924. Nonparametric analyses further supported the presence of a locus on chromosome 4q35. A maximum score of 2.62 (P=.01) was obtained between D4S1652 and D4S171 by use of the GENEHUNTER program, and a maximum score of 3.57 (P=.0002) was obtained at D4S2924 using the affected pedigree member method. Analysis of a further 10 pedigrees suggests the presence of this locus in at least one additional family, indicating a possible predisposing locus and not a pedigree-specific mutation. Our results suggest the presence of a novel BAD susceptibility locus on chromosome 4q35.
Bipolar Disorder↗
Use of psychotropic medications in breast-feeding women: acute and prophylactic treatment.
OBJECTIVES: The postnatal period is a time of increased onset and relapse of mental illness. It poses a clinical dilemma, as many mothers requiring medication acutely or prophylactically will also choose to breast feed. The present paper first reviews the safety of psychotropes in breast-fed infants and the usefulness of prophylaxis for women at risk of postpartum affective relapse and, second, provides guidelines in the use of psychotropic drugs in breast-feeding women. METHODS: A Medline review was conducted reviewing all papers published during the period 1993-1998 (and their associated bibliographies) on the use of psychotropes in breast-feeding women and the prophylactic usefulness of medications in women at risk of affective postpartum relapse. RESULTS: Findings are based on case reports and small, mostly uncontrolled studies. Both tricyclic antidepressants (TCA) and specific serotonin re-uptake inhibitors (SSRIs) appear to be relatively safe in breast feeding. Antidepressants commenced in the early postpartum period may reduce depressive relapse. While prophylactic lithium appears to significantly reduce relapse of affective psychosis in the puerperium, there have been no studies of the anticonvulsants in the puerperium. Finally, high dose antipsychotics should be avoided, as they may be associated with long-term adverse sequelae in the infant. CONCLUSIONS: On the basis of current knowledge, the use of SSRIs, TCA, carbamazepine, sodium valproate and short-acting benzodiazepines in breast feeding is relatively safe. If lithium is to be used, close collaboration with a paediatrician is essential. The long-term risks of antipsychotics, especially at high doses, remain to be clarified. Before a decision can be made, the risk-benefit ratio must be clearly outlined and discussed with the mother and her partner.
Antidepressive Agents, Tricyclic↗