Depression: Anderson IM

Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G, Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A. · Senior Lecturer and Honorary Consultant Psychiatrist, Neuroscience and Psychiatry Unit, University of Manchester, UK. · J Psychopharmacol. · Pubmed #18413657 No free full text.

Abstract: A revision of the 2000 British Association for Psychopharmacology evidence-based guidelines for treating depressive disorders with antidepressants was undertaken to incorporate new evidence and to update the recommendations where appropriate. A consensus meeting involving experts in depressive disorders and their management was held in May 2006. Key areas in treating depression were reviewed, and the strength of evidence and clinical implications were considered. The guidelines were drawn up after extensive feedback from participants and interested parties. A literature review is provided, which identifies the quality of evidence to inform the recommendations, the strength of which are based on the level of evidence. These guidelines cover the nature and detection of depressive disorders, acute treatment with antidepressant drugs, choice of drug versus alternative treatment, practical issues in prescribing and management, next-step treatment, relapse prevention, treatment of relapse, and stopping treatment.

Anderson IM, Nutt DJ, Deakin JF. · University of Manchester Department of Psychiatry, University of Manchester, UK. · J Psychopharmacol. · Pubmed #10757248 No free full text.

Abstract: 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.

Anderson IM. · Neuroscience and Psychiatry Unit, School of Psychiatry and Behavioural Sciences, University of Manchester, UK. · Br Med Bull. · Pubmed #11719915 No free full text.

Abstract: A systematic search found 108 meta-analyses of the use of antidepressants in depressive disorders. Defining newer antidepressants as those introduced since the early 1980s, 18 meta-analyses were selected as being informative about their relative efficacy and tolerability in comparative randomised controlled studies (RCTs). Findings with higher confidence include: little difference in efficacy between most new and old antidepressants; superior efficacy of serotonin and noradrenaline re-uptake inhibitors (SNRIs) over selective serotonin re-uptake inhibitors (SSRIs); a slower onset of therapeutic action of fluoxetine over other SSRIs; a different side effect profile of SSRIs to TCAs with superior general tolerability of SSRIs over TCAs; poorer tolerability of fluvoxamine than other SSRIs in a within group comparison; no increased the risk of suicidal acts or ideation in fluoxetine compared with TCAs (or placebo) in low-risk patients. Findings with a lower level of confidence include: greater efficacy of TCAs than SSRIs in in-patients; greater efficacy of amitriptyline than SSRIs; better tolerability of moclobemide than TCAs; no demonstrable difference in tolerability between SSRIs and TCAs in the elderly; no better tolerability of fluvoxamine than TCAs; better tolerability of dothiepin (dosulepin) than SSRIs; better tolerability of sertraline and greater frequency of agitation on fluoxetine than other SSRIs in a within group comparison. In general, the meta-analyses were of uneven quality, as were the studies included, which limits the confidence in many of the results. Generalising from mostly short-term randomised controlled studies to clinical practice requires caution.

Völlm B, Richardson P, McKie S, Elliott R, Deakin JF, Anderson IM. · Neuroscience and Psychiatry Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK. · Eur J Neurosci. · Pubmed #16420462 No free full text.

Abstract: Serotonin (5-HT) has been implicated in the aetiology of a number of psychiatric conditions, including depression, anxiety and antisocial personality disorder. The development of these disorders may arise from alterations in underlying motivational and cognitive processes such as emotional recognition, reinforcement processing and central inhibitory control. This study aimed to localize where in the brain 5-HT modulates neuropsychological processes relevant to putative 5-HT disorders, using functional magnetic resonance imaging. We examined the effect of the antidepressant mirtazapine on brain activations associated with behavioural inhibition and reinforcement processing in healthy subjects. Forty-five men were randomly allocated to receiving mirtazapine or placebo in a double-blind fashion. A Go/No-Go, Reward/No-Reward and Loss/No-loss task were performed during functional magnetic resonance imaging using a 1.5 Tesla Philips Gyroscan scanner. Blood oxygenation level dependent (BOLD) responses were analysed using SPM2. Task activations were largely consistent with previous findings. Mirtazapine modulated brain activations in the Go/No-Go and Reward/No-Reward task. During behavioural inhibition, enhanced activations were observed in the right orbitofrontal cortex (BA47). Increased activations in bilateral parietal cortex were found during the Reward task while no significant interaction was observed in the Loss task. Our results support the suggestion of an important role of serotonin in modulating basic processes involved in psychiatric disorders. Combining drug challenge with fMRI (pharmacoMRI; pMRI) is a promising tool for investigating these processes in healthy as well as patient groups.

Del-Ben CM, Deakin JF, McKie S, Delvai NA, Williams SR, Elliott R, Dolan M, Anderson IM. · Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. · Neuropsychopharmacology. · Pubmed #15827569 links to  free full text

Abstract: Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders, depression, and anxiety. We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders. In all, 12 male volunteers received citalopram (7.5 mg intravenously) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go, Loss/No-loss, and covert (aversive) face emotion recognition tasks during functional magnetic resonance imaging (fMRI). Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping (SPM2). The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex (BA47) common to the three tasks. Citalopram pretreatment enhanced the right BA47 responses to the No-go condition, but attenuated this response to aversive faces. Attenuations were seen following citalopram in the medial orbitofrontal (BA11) responses to the No-go and No-loss (ie relative reward compared with Loss) conditions. The right amygdala response to aversive faces was attenuated by citalopram. These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific, rather than general effect. The technique of combining drug challenge with fMRI (pharmacoMRI) has promise for investigating human psychiatric disorders.

Richell RA, Deakin JF, Anderson IM. · Psychiatry Group, Medical Research Council Clinical Sciences Centre, Imperial College, London. · Biol Psychiatry. · Pubmed #15691531 No free full text.

Abstract: BACKGROUND: Previous research provides evidence linking serotonin (5-hydroxytryptamine, 5-HT) with stress and depression. The controllable/uncontrollable (C/UC) stress paradigm aims to generate a state/condition, namely a feeling of lack of control in the context of a stressor, which might be an important factor in precipitating a negative mood state. Acute tryptophan depletion (ATD) is a technique that produces a decrease in central 5-HT levels in vivo. This study investigated the role of 5-HT in the behavioral response to a C/UC stress paradigm with ATD. METHODS: Healthy adult volunteers were randomly assigned to receive either a TRP-supplemented (n = 15) or TRP-deficient (n = 13) amino acid drink. At 5 hours postdrink, volunteers were subjected to sessions of controllable and uncontrollable noise stress (100-dB white noise). Subjective ratings of mood were obtained before and after the interventions. RESULTS: Participants who received the tryptophan-depleting drink had greater self-report ratings of negative mood on visual analogue scales and the Profile of Mood States after the uncontrollable stress than did participants who received the balanced drink. CONCLUSIONS: The results suggest that 5-HT might play a role in providing resilience to uncontrollable stress. Additional studies with specific 5-HT pharmacologic probes will further clarify the results.

Juhasz G, Lazary J, Chase D, Pegg E, Downey D, Toth ZG, Stones K, Platt H, Mekli K, Payton A, Anderson IM, Deakin JF, Bagdy G. · Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK. · Neurosci Lett. · Pubmed #19539700 No free full text.

Abstract: In animal models endogenous cannabinoids have an inhibitory effect on trigeminovascular activation through the cannabinoid receptor 1 (CB1), although there is no evidence of the potential role of CB1 in human migraine. In this study we applied single marker association and haplotypic trend regression analysis to investigate the relationship between the CB1 gene (CNR1) and headache with migraine symptoms (nausea, photophobia and disability, measured by the ID-migraine questionnaire). We identified our controls (CO=684) as those who have not reported ID-migraine symptoms at all and defined migraine headache sufferers (M=195) as those who reported all three symptoms. The CNR1 was covered by 10 SNPs located throughout the gene based on haplotype tagging (htSNP) and previous literature. Our results demonstrated a significant haplotypic effect of CNR1 on migraine headaches (p=0.008, after permutation p=0.017). This effect was independent of reported depression or drug/alcohol abuse although using neuroticism in the analysis as covariant slightly decreased this association (p=0.027, permutated p=0.052). These results suggest a significant effect of CNR1 on migraine headaches that might be related to the alteration of peripheral trigeminovascular activation. In addition, this is the first study to demonstrate the effectiveness of using trait components combinations to define extreme phenotypes with haplotype analysis in genetic association studies for migraine. However, further studies are needed to elucidate the role of CNR1 and the cannabinoid system in migraine.

Juhasz G, Chase D, Pegg E, Downey D, Toth ZG, Stones K, Platt H, Mekli K, Payton A, Elliott R, Anderson IM, Deakin JF. · Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK. · Neuropsychopharmacology. · Pubmed #19242408 No free full text.

Abstract: Cannabinoid receptor 1 (CB1) gene (CNR1) knockout mice are prone to develop anhedonic and helpless behavior after chronic mild stress. In humans, the CB1 antagonist rimonabant increases the risk of depressed mood disorders and anxiety. These studies suggest the hypothesis that genetic variation in CB1 receptor function influences the risk of depression in humans in response to stressful life events. In a population sample (n=1269), we obtained questionnaire measures of personality (Big Five Inventory), depression and anxiety (Brief Symptom Inventory), and life events. The CNR1 gene was covered by 10 SNPs located throughout the gene to determine haplotypic association. Variations in the CNR1 gene were significantly associated with a high neuroticism and low agreeableness phenotype (explained variance 1.5 and 2.5%, respectively). Epistasis analysis of the SNPs showed that the previously reported functional 5' end of the CNR1 gene significantly interacts with the 3' end in these phenotypes. Furthermore, current depression scores significantly associated with CNR1 haplotypes but this effect diminished after covariation for recent life events, suggesting a gene x environment interaction. Indeed, rs7766029 showed highly significant interaction between recent negative life events and depression scores. The results represent the first evidence in humans that the CNR1 gene is a risk factor for depression--and probably also for co-morbid psychiatric conditions such as substance use disorders--through a high neuroticism and low agreeableness phenotype. This study also suggests that the CNR1 gene influences vulnerability to recent psychosocial adversity to produce current symptoms of depression.

Anderson IM, Sarsfield A, Haddad PM. · Manchester Mental Health and Social Care Trust/University of Manchester, United Kingdom. · J Affect Disord. · Pubmed #19171384 No free full text.

Abstract: BACKGROUND: Atypical antipsychotics may have efficacy as augmentation therapy in treatment resistant depression (TRD) but evidence is limited. METHODS: An open label study of quetiapine augmentation in 24 patients (mean age: 46.3 years) with a DSM-IV major depressive episode resistant to at least 2 trials of antidepressant medication, and currently taking a monoamine reuptake inhibitor. An 8-week treatment phase was followed by an 18-week extension in patients who showed clinical benefit. RESULTS: Eighteen patients (75%) completed the 8-week treatment phase with seven patients (29%) being responders on the Montgomery Asberg Depression Rating Scale and 13 (54%) on the CGI-I. Fewer patients responded if they had previously received olanzapine in the current episode but this was not statistically significant (0% v 37%, p=0.27). Of the eleven patients entering the extension phase, 3 patients (27%) experienced a significant worsening of mood. The most common adverse events were sedation (54%), dry mouth (38%) and dizziness (29%). Significant weight gain was found in 40% of patients treated for 26 weeks. Average quetiapine doses were 245 mg at 8 weeks and 346 mg at 26 weeks. CONCLUSIONS: Quetiapine may be a helpful adjunctive agent for some patients with TRD but placebo-controlled trials are needed to establish its place in management. LIMITATIONS: The trial was open-label and the numbers were small.

Tint A, Haddad PM, Anderson IM. · Bolton, Trafford & Salford Mental Health NHS Trust, Kenyon House, Prestwich Hospital, Bury New Road, Manchester M25 3BL, UK. · J Psychopharmacol. · Pubmed #18515448 No free full text.

Abstract: 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' ( > or = 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.

Anderson IM, Delvai NA, Ashim B, Ashim S, Lewin C, Singh V, Sturman D, Strickland PL. · Neuroscience and Psychiatry Unit, University of Manchester, Manchester, UK. · Br J Psychiatry. · Pubmed #17541116 links to  free full text

Abstract: The place of repetitive transcranial magnetic stimulation (rTMS) in the treatment of depression remains unclear. In this sham-controlled study we determined the efficacy and acceptability offast, left frontal rTMS given three times a week over 4-6 weeks to 29 patients with depression (79% treatment-resistant). The procedure was generally well tolerated and more effective than sham treatment (55 v.77% responding, P<0.05), with improvement maintained to 12 weeks. This therapy could be a useful addition to available treatments but further research is needed to determine the optimum treatment parameters.

Argyropoulos SV, Ploubidis GB, Wright TS, Palm ME, Hood SD, Nash JR, Taylor AC, Forshall SW, Anderson IM, Nutt DJ, Potokar JP. · Psychopharmacology Unit, Dorothy Hodgkin Building, Whiston Street, Bristol, UK. · J Psychopharmacol. · Pubmed #17329293 No free full text.

Abstract: The psychometric tools used for the assessment of generalized anxiety disorder (GAD) either do not conform to the current concept of the condition or have important limitations. We aimed to develop and validate a new questionnaire for the assessment of symptom profile and severity of GAD.An original pool of potential scale items was subjected to a series of studies in non-clinical and clinical populations, in order to determine the final composition of the scale. The psychometric properties of the new scale, the Generalized Anxiety Disorder Inventory (GADI), were evaluated using a factor analytic model suitable for ordinal data and the Graded Response Model. The precision of measurement of the GADI was quantified through the item information functions.A total of 197 outpatients and 522 non-clinical subjects participated in four studies and completed the GADI. The final 18-item scale was derived from an original pool of 30 potential items. The GADI showed good reliability, convergent and divergent validity. The scale comprises three factors, relating to cognitive, somatic and sleep symptoms. It accurately distinguished GAD patients from non-patient controls. The cognitive factor also distinguished GAD from other anxiety disorders and depression.The GADI is a useful tool in the assessment of the breadth of symptoms and the severity of generalized anxiety disorder in clinical settings.

Parker G, Anderson IM, Haddad P. · School of Psychiatry, University of New South Wales, Australia. · Br J Psychiatry. · Pubmed #12893662 links to  free full text

This publication has no abstract.

Freemantle N, Anderson IM, Young P. · Medicines Evaluation Group, Centre for Health Economics, University of York, Heslington, York YO10 5DD, UK. · Br J Psychiatry. · Pubmed #11116769 links to  free full text

Abstract: BACKGROUND: There is uncertainty about the contribution of specific pharmacological properties to the efficacy of antidepressants. AIMS: To assess whether specific pharmacological characteristics of alternative antidepressants resulted in altered efficacy compared to that of selective serotonin reuptake inhibitors in the treatment of major depression. METHOD: Meta-regression analysis of randomised trials that compare treatment with a selective serotonin reuptake inhibitor and an alternative antidepressant. RESULTS: One-hundred-and-five randomised trials were included. None of the factors identified a priori predicted a statistically significant improvement in outcome across the trials. CONCLUSIONS: This analysis does not provide evidence that antidepressants acting at more than one pharmacological site differ in efficacy from drugs selective for serotonin reuptake in the treatment of major depression.

Anderson IM. · Neuroscience and Psychiatry Unit, Room G809, Stopford Building, University of Manchester, Oxford Road, Manchester, UK. · J Affect Disord. · Pubmed #10760555 No free full text.

Abstract: Background: A meta-analysis of the efficacy and tolerability of selective serotonin reuptake inhibitors (SSRIs) against tricyclic antidepressants (TCAs) in depressed patients was carried out. Methods: Efficacy data from 102 randomised controlled trials (10706 patients) were pooled to provide a summary variance-weighted effect size. Tolerability data from 95 studies (10553 patients) were combined to give variance-weighted relative risk of drop out for all reasons and for adverse effects from each study. The effect of age, treatment setting, severity and TCA dose were examined as well as the performance of individual SSRIs and TCAs where there were sufficient studies. Results: There is no overall difference in efficacy between SSRIs and TCAs (effect size -0.03, 95% confidence interval -0.09 to 0.03). TCAs do appear more effective in in-patients (-0.23, -0.40 to -0.05) and amitriptyline is more effective than SSRI comparators (-0.14, -0.25 to -0.03) but publication bias cannot be excluded. The SSRIs are better tolerated, with significantly lower rates of treatment discontinuations overall (relative risk 0.88, 0.83 to 0.93; number needed to treat 26) and due to side effects (0.73, 0.67 to 0.80; number needed to treat 33). Individual SSRIs show a similar advantage except for fluvoxamine which does not differ from the TCAs. Individual TCAs show a similar disadvantage in tolerability compared to SSRIs except for dothiepin against which SSRI treatment results in more side-effect related drop outs (2.64, 1.50 to 4.63; number needed to harm 12). Limitations: The evidence is from short-term studies and subgroup analyses may result in chance results. Conclusions: Overall efficacy between the two classes is comparable but SSRIs are not proven to be as effective as TCAs in in-patients and against amitriptyline. SSRIs have a modest advantage in terms of tolerability against most TCAs.

Anderson IM, Haddad PM. · No affiliation provided · Br J Psychiatry. · Pubmed #12777351 links to  free full text

This publication has no abstract.