About one-third of patients fail to respond to initial antidepressant therapy, which suggests a need for more effective drugs.

To compare the efficacy and safety of venlafaxine and paroxetine in 122 patients with non-chronic treatment-resistant depression.

In-patients or out-patients satisfying DSM – III – R criteria for major depression in evolution for less than eight months, having a baseline HAM–D score 18 and a HAM – D Item 3 score < 3 were eligible. Patients were required to have a history of resistance to two previous antidepressant treatments and a CGI improvement score of 3 at the beginning of treatment. Doses were adjusted to 200–300 mg/day for venlafaxine and 30–40 mg/day for paroxetine.

For the observed-case analysis, the response rate was 51.9% for venlafaxine and 32.7% for paroxetine (P=0.044), and a remission was achieved in 42.3% of venlafaxine-treated and 20.0% of paroxetine-treated patients (P=0.01). The incidence of adverse effects was comparable between treatment groups.

Venlafaxine showed some evidence of superiority to paroxetine in this difficult-to-treat patient population.

Psilocybin is a classic psychedelic drug that has a history of use in psychotherapy. One of the rationales for its use was that it aids emotional insight by lowering psychological defences.

To test the hypothesis that psilocybin facilitates access to personal memories and emotions by comparing subjective and neural responses to positive autobiographical memories under psilocybin and placebo.

Ten healthy participants received two functional magnetic resonance imaging scans (2mg intravenous psilocybin v. intravenous saline), separated by approximately 7 days, during which they viewed two different sets of 15 positive autobiographical memory cues. Participants viewed each cue for 6 s and then closed their eyes for 16 s and imagined re-experiencing the event. Activations during this recollection period were compared with an equivalent period of eyes-closed rest. We split the recollection period into an early phase (first 8 s) and a late phase (last 8 s) for analysis.

Robust activations to the memories were seen in limbic and striatal regions in the early phase and the medial prefrontal cortex in the late phase in both conditions (P<0.001, whole brain cluster correction), but there were additional visual and other sensory cortical activations in the late phase under psilocybin that were absent under placebo. Ratings of memory vividness and visual imagery were significantly higher after psilocybin (P<0.05) and there was a significant positive correlation between vividness and subjective wellbeing at follow-up (P<0.01).

Evidence that psilocybin enhances autobiographical recollection implies that it may be useful in psychotherapy either as a tool to facilitate the recall of salient memories or to reverse negative cognitive biases.

Public stigma against people with mental health problems is damaging to individuals with mental illness and is associated with substantial societal burden.

To investigate whether public knowledge, attitudes and behaviour in relation to people with mental health problems have improved among the English population since the inception of the Time To Change programme in 2009.

We analysed longitudinal trends in public knowledge, attitudes and behaviour between 2009 and 2012 among a nationally representative sample of English adults.

There were improvements in intended behaviour (0.07 standard deviation units, 95% CI 0.01-0.14) and a nonsignificant trend for improvement in attitudes (P=0.08) among the English population. There was, however, no significant improvement in knowledge or reported behaviour.

The findings provide support for effectiveness of the national Time to Change programme against stigma and discrimination in improving attitudes and intended behaviour, but not knowledge, among the public in England.

Anxiety and depression are common in people with dementia and mild cognitive impairment (MCI), but there is uncertainty about the effectiveness of both pharmacological and psychological therapies.

To evaluate the evidence of effectiveness of psychological treatments in treating depression and anxiety in people with dementia and MCI.

We carried out a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological treatment versus usual care in people with dementia and MCI. Primary outcomes were symptoms of anxiety and depression. Secondary outcomes were quality of life, ability to perform daily activities, neuropsychiatric symptoms, cognition and caregivers' self-rated depressive symptoms.

We included six RCTs, involving 439 participants with dementia, which used cognitive–behavioural therapy, interpersonal therapy, counselling or multimodal interventions including a specific psychological therapy. We found beneficial effects for both depression and anxiety. Overall, the quality of the evidence was moderate for depression and low for anxiety, due to the methodological limitations of the studies we identified and the limited number of trials.

The evidence from six RCTs suggests that psychological treatments are effective in reducing symptoms of depression and anxiety for people with dementia. There is a need for high-quality, multicentre trials including standardised, well-defined interventions.

A.Q., A.S. and M.O. are investigators in one of the included studies.

A randomised controlled trial comparing group interpersonal psychotherapy with treatment as usual among rural Ugandans meeting symptom and functional impairment criteria for DSM–IV major depressive disorder or sub-threshold disorder showed evidence of effectiveness immediately following the intervention.

To assess the long-term effectiveness of this therapy over a subsequent 6-month period.

A follow-up study of trial participants was conducted in which the primary outcomes were depression diagnosis, depressive symptoms and functional impairment.

At 6 months, participants receiving the group interpersonal psychotherapy had mean depression symptom and functional impairment scores respectively 14.0 points (95% CI 12.2–15.8; P < 0.0001) and 5.0 points (95% CI 3.6–6.4; P < 0.0001) lower than the control group. Similarly, the rate of major depression among those in the treatment arm (11.7%) was significantly lower than that in the control arm (54.9%) (P < 0.0001).

Participation in a 16-week group interpersonal psychotherapy intervention continued to confer a substantial mental health benefit 6 months after conclusion of the formal intervention.

Violence is an uncommon but significant problem associated with schizophrenia

To compare antipsychotic medications in reducing violence among patients with schizophrenia over 6 months, identify prospective predictors of violence and examine the impact of medication adherence on reduced violence

Participants (n=1445) were randomly assigned to double-blinded treatment with one of five antipsychotic medications. Analyses are presented for the intention-to-treat sample and for patients completing 6 months on assigned medication

Violence declined from 16% to 9% in the retained sample and from 19% to 14% in the intention-to-treat sample. No difference by medication group was found, except that perphenazine showed greater violence reduction than quetiapine in the retained sample. Medication adherence reduced violence, but not in patients with a history of childhood antisocial conduct. Prospective predictors of violence included childhood conduct problems, substance use, victimisation, economic deprivation and living situation. Negative psychotic symptoms predicted lower violence

Newer antipsychotics did not reduce violence more than perphenazine. Effective antipsychotics are needed, but may not reduce violence unrelated to acute psychopathology

A randomised controlled trial of cognitive — behavioural therapy (CBT) for people with medication-resistant psychosis showed improvements in overall symptomatology after nine months of treatment; good outcome was strongly predicted by a measure of cognitive flexibility concerning delusions. The present paper presents a follow-up evaluation 18 months after baseline.

Forty-seven (78% of original n=60) participants were available for follow-up at 18 months, and were reassessed on all the original outcome measures (see Part I). An economic evaluation was also completed.

Those in the CBT treatment group showed a significant and continuing improvement in Brief Psychiatric Rating Scale scores, whereas the control group did not change from baseline. Delusional distress and the frequency of hallucinations were also significantly reduced in the CBT group. The costs of CB Tappear to have been offset by reductions in service utilisation and associated costs during follow-up.

Improvement in overall symptoms was maintained in the CBT group 18 months after baseline and nine months after intensive therapy was completed. CBT may be a specific and cost-effective intervention in medication-resistant psychosis.

Tricyclic antidepressants and serotonin reuptake inhibitors are considered to be equally effective, but differences may have been obscured by internally inconsistent measurement scales and inefficient statistical analyses.

To test the hypothesis that escitalopram and nortriptyline differ in their effects on observed mood, cognitive and neurovegetative symptoms of depression.

In a multicentre part-randomised open-label design (the Genome Based Therapeutic Drugs for Depression (GENDEP) study) 811 adults with moderate to severe unipolar depression were allocated to flexible dosage escitalopram or nortriptyline for 12 weeks. The weekly Montgomery–Åsberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Beck Depression Inventory were scored both conventionally and in a more novel way according to dimensions of observed mood, cognitive symptoms and neurovegetative symptoms.

Mixed-effect linear regression showed no difference between escitalopram and nortriptyline on the three original scales, but symptom dimensions revealed drug-specific advantages. Observed mood and cognitive symptoms improved more with escitalopram than with nortriptyline. Neurovegetative symptoms improved more with nortriptyline than with escitalopram.

The three symptom dimensions provided sensitive descriptors of differential antidepressant response and enabled identification of drug-specific effects.

Recent research from North America has demonstrated higher than expected rates of drug and alcohol abuse among the seriously mentally ill. Schizophrenics appear to be particularly susceptible to the negative effects of substance abuse. These include psychiatric and social complications, with antisocial behaviour, particularly violence emerging as one of the most worrying features. This review examines the strength of the association and explores the possible explanations for the apparent link between schizophrenia, substance abuse and violence.

The literature was searched using Medline, supplemented with a manual literature search.

Very few articles specifically approached the problem of violence among substance abusing schizophrenics, but over 80 papers were identified which were helpful in exploring the link between dangerous behaviour and substance abuse by schizophrenics.

While there is circumstantial evidence to support the hypothesis that schizophrenics who abuse drugs or alcohol are at an increased risk of behaving violently, longitudinal studies are required to facilitate a better understanding of the mediating mechanisms.