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Background: There is a lack of evidence to guide treatment of comorbid depression and anxiety. Preliminary evidence suggests mirtazapine may be effective in treating patients with both depression and anxiety symptoms. Methods: We undertook a secondary analysis of mirtazapine (MIR): a placebo-controlled trial of the addition of mirtazapine to a selective serotonin reuptake inhibitor or serotonin–norepinephrine reuptake inhibitor in treatment-resistant depression (TRD) in primary care. We subdivided participants into three groups by baseline generalized anxiety disorder score (GAD-7): severe (GAD-7 ⩾ 16), moderate (GAD-7 = 11–15), no/mild (GAD-7 ⩽ 10). We used linear regression including likelihood-ratio testing of interaction terms to assess how baseline anxiety altered the response of participants to mirtazapine as measured by 12-week GAD-7 and Beck Depression Inventory II (BDI-II) scores. Results: Baseline generalized anxiety moderated mirtazapine’s effect as measured by GAD-7 ( p = 0.041) and BDI-II ( p = 0.088) at 12 weeks. Participants with severe generalized anxiety receiving mirtazapine had lower 12-week GAD-7 score (adjusted difference between means (ADM) −2.82, 95% confidence interval (CI) −0.69 to −4.95) and larger decreases in BDI-II score (ADM −6.36, 95% CI −1.60 to −10.84) than placebo. Conversely, there was no anxiolytic benefit (ADM 0.28, 95% CI −1.05 to 1.60) or antidepressant benefit (ADM −0.17, 95% CI −3.02 to 2.68) compared with placebo in those with no/mild generalized anxiety. Conclusions: These findings extend the evidence for the effectiveness of mirtazapine to reduce generalized anxiety in TRD in primary care. These results may inform targeted prescribing in depression based on concurrent anxiety symptoms, although these conclusions are constrained by the post-hoc nature of this analysis.

Background: A quality improvement programme addressing prescribing practice for depression was initiated by the Prescribing Observatory for Mental Health. Methods: A baseline clinical audit against evidence-based practice standards was conducted in UK adult mental health services. Results: A total of 55 mental health services submitted data for 2082 patients, under the care of a community psychiatric team (CMHT) for at least a year, with a diagnosis of moderate or severe unipolar depression, 54% of whom had a comorbid psychiatric diagnosis. Selective serotonin reuptake inhibitors were prescribed for 35% of the patients, other newer generation antidepressants for 60%, tricyclic antidepressants for 6% and monoamine oxidase inhibitors for Conclusion: Patients with moderate or severe depression remaining under the care of a CMHT for longer than a year are clinically complex. The failure to achieve a level of wellness allowing discharge from mental health services may be partly related to the finding that not all patients had the benefit of a systematic approach to clinical assessment and sequential testing of available evidence-based pharmacological interventions.

Delay discounting and probability discounting tasks providing hypothetical rewards have commonly been used to measure levels of impulsivity and risk taking. Results have been inconsistent as to whether real, compared with hypothetical, rewards influence choice behaviour in delay discounting tasks. This experiment examined choice behaviour in 38 healthy individuals using delay and probability discounting tasks involving both real and hypothetical rewards (pound sterling 0.10/pound sterling 0.20), real delays, and probabilistic outcomes. It was hypothesized that choice behaviour when receiving real rewards would be less impulsive and less risky than when receiving hypothetical rewards. The tasks were designed so that a mathematical model (the multiplicative hyperbolic model of choice) could be applied to assess effects on discounting parameters. The provision of real rewards was associated with significantly decreased impulsive, but not risky, choice although the size of effect was small and was influenced by the order of presentation. Repeated presentation of both tasks increased quantity discounting but not delay or probability discounting parameters. These results indicate that the nature of the reward provided, and repetition effects, need to be taken into account when designing discounting studies.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Acute dietary tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture (TP-). The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the TP-occasion (-78.7%, p < 0.0001) and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions ( p < 0.02). Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.

In spite of conflicting reports, there is emerging evidence that at least two of the atypical antipsychotics, clozapine and olanzapine, are associated with an increased risk of developing glucose dysregulation or new onset diabetes mellitus. We report on the management of six patients who developed diabetes mellitus following treatment with olanzapine, five of whom had independent risk factors for diabetes. Olanzapine was changed to quetiapine in all patients with improvement in glycaemic control in two patients. In view of the uncertainty of the size and mechanism of the link between olanzapine and diabetes, we discuss issues surrounding routine clinical management and monitoring of patients on antipsychotics and the clinical implications.

Reduced serotonergic (5-HT) neurotransmission has been reported in impulsive and aggressive personality disordered and offender samples. What is not clear is the relationship between 5-HT function and the North American construct of psychopathy assessed using the Psychopathy Checklist and its derivatives, which emphasizes the core interpersonal/affective as well as behavioural components of this syndrome. Fifty-one DSM-III-R personality disordered offenders who had a dynamic assessment of 5-HT function (prolactin response to 30 mg d-fenfluramine challenge) were rated on the Psychopathy Checklist: Screening Version based on interview and file data. The Psychopathy Checklist: Screening Version (PCL: SV) mean score in the sample was similar to other reports in European forensic samples. A three-factor structure best explained the PCL: SV data: arrogant/deceitful, callous-unemotional and impulsive-antisocial behaviour factors. 5-HT function did not correlate with psychopathy as a unidimensional phenomenon. The impulsive-antisocial component correlates negatively with 5-HT function while the arrogant/deceitful component correlates positively with 5-HT. In line with previous research findings, impulsive-antisocial conduct shows an inverse relationship with 5-HT function. Arrogant/deceitful traits correlate positively with 5-HT function and may be an adaptive component of psychopathy.

Choice behaviour can be viewed as a response to reinforcement determined by an interaction between the quantities, delays and probabilities of two outcomes. The variation in the perceived value of a reinforcer with alteration of these factors (discounting) can be modelled mathematically by hyperbolic discounting functions. Making risky choices is a feature of impulsivity and has been associated with reduced serotonin (5-hydroxytryptamine, 5-HT) function. In this study, we investigated the possible role of 5-HT in modulating probability discounting using the technique of acute tryptophan (TRP) depletion in subjects undertaking an imaginary gambling task. The gambling task consisted of choosing between two ‘roulette-like’ dials: ‘A’ which provided a smaller but nearly certain ‘win’ and ‘B’ which gave a ‘win’ 2.5 times the amount with a probability that was systematically varied. A series of reward sizes on dial ‘A’ was presented ranging from 10 pence to £10 000. The probability of winning on dial ‘B’ at which the subjects valued the two dials equally (indifference point) was determined as a measure of willingness to take a risk. Subjects were more likely to take a risk for smaller rewards but the indifference points in the 15 subjects who received TRP depletion did not differ from 13 who had the control drink. On a surprise retesting 1 week later there was a trend (p < 0.07) for subjects to be more willing to take risks the second time, particularly in the case of small rewards. This study does not support a role for 5-HT in modulating probabilistic choice in agreement with recent evidence from experiments with animals; however, the imaginal nature of the task and modest numbers may have influenced the result.

A revision of the British Association for Psychopharmacology guidelines for treating depressive disorders with antidepressants was undertaken in order to specify the scope and target of the guidelines and to update the recommendations based explicitly on the available evidence. A consensus meeting, involving experts in depressive disorders and their treatment, reviewed key areas and considered the strength of evidence and clinical implications. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is given which identifies the quality of evidence followed by recommendations, the strength of which are based on the level of evidence. The guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing, management when initial treatment fails, continuation treatment, maintenance treatment to prevent recurrence and stopping treatment.

Twenty eight patients treated with selective serotonin reuptake inhibitors /venlafaxine were randomized to a three-day (short) or 14-day (longer) anti—depressant taper and openly assessed after a five to seven day drug-free washout, and again after seven days treatment with a new anti—depressant of the treating clinician's choice. A 'discontinuation syndrome' ( ≥ 3 new symptoms on the Discontinuation Emergent Signs and Symptoms checklist) occurred in 46% of patients with a similar frequency in those with short (7/15) versus longer (6/13) taper. Patients initially on short half-life anti—depressants had significantly greater increases in discontinuation and depressive symptoms than those stopping fluoxetine. Four patients, all on paroxetine, developed emergent suicidal ideation after taper. These results support the importance of half-life in determining discontinuation symptoms and suggest that there is little advantage to a two-week taper over a three-day taper when switching antidepressants. Antidepressant discontinuation in depressed patients can be associated with worsening depression and increased suicidality.

A Tint, P M Haddad, and I M Anderson. The effect of rate of antidepressant tapering on the incidence of discontinuation symptoms: a randomised study. Journal of Psychopharmacology first published this on May 30, 2008 as DOI: 10.1177/0269881107087488. This version is no longer available. The version of record is published in Vol. 22 No 3, DOI 10.1177/0269881107081550