There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.

We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.

We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.

Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).

These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.

Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).

To reach consensus regarding threshold definitions criteria for TRBD and MTRBD.

Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method.

TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy.

The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.

In the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

Clinical trials have examined the efficacy of drugs to prevent relapse in patients with bipolar disorder, however, their design often limits generalisation to routine clinical practice.

To estimate the effectiveness of drugs used for maintenance treatment in bipolar disorder.

We used national registers to identify 35022 individuals diagnosed with bipolar disorder and information on lithium, valproate, carbamazepine, lamotrigine, quetiapine and olanzapine treatment from 2006 to 2009. The main outcome was psychiatric hospital admissions. We used stratified cox regression to compare periods on and off medication within the same individual.

Medication with lithium, valproate, lamotrigine, olanzapine and quetiapine was associated with reduced rates of admission to hospital. Lithium was more effective than quetiapine and olanzapine. The effects of specific drugs depended on the polarity of the mood episode.

Our findings complement results from randomised controlled trails, but suggest that lithium is more effective than both quetiapine and olanzapine in routine clinical practice.

Adjunctive antidepressant therapy is commonly used to treat acute bipolar depression but few studies have examined this strategy.

To examine the efficacy of agomelatine v. placebo as adjuncts to lithium or valproate in bipolar depression.

Patients who were currently depressed despite taking lithium or valproate for at least 6 weeks were randomised to treatment with agomelatine (n = 172) or placebo (n = 172) for 8 weeks of acute therapy and 44 weeks of continuation therapy (trial registration: ISRCTN28588282).

No significant differences in improvement of depressive symptoms were observed between the two groups either at 8 weeks or 52 weeks on the primary efficacy measure of change in Montgomery–Åsberg Depression Rating Scale scores from baseline to end-point. Adverse events including switches into mania/hypomania were low and similar in both groups.

Agomelatine adjunctive therapy was not superior to placebo adjunctive therapy for acute bipolar depression.

North American studies show bipolar disorder is associated with elevated rates of problem gambling; however, little is known about rates in the different presentations of bipolar illness.

To determine the prevalence and distribution of problem gambling in people with bipolar disorder in the UK.

The Problem Gambling Severity Index was used to measure gambling problems in 635 participants with bipolar disorder.

Moderate to severe gambling problems were four times higher in people with bipolar disorder than in the general population, and were associated with type 2 disorder (OR = 1.74, P = 0.036), history of suicidal ideation or attempt (OR = 3.44, P = 0.02) and rapid cycling (OR = 2.63, P = 0.008).

Approximately 1 in 10 patients with bipolar disorder may be at moderate to severe risk of problem gambling, possibly associated with suicidal behaviour and a rapid cycling course. Elevated rates of gambling problems in type 2 disorder highlight the probable significance of modest but unstable mood disturbance in the development and maintenance of such problems.

People with intellectual disabilities have a high risk of osteoporosis and fractures, which could partly be as a result of vitamin D deficiency.

To compare the serum vitamin D (25(OH)D) levels of 155 patients with intellectual disabilities under psychiatric care and 192 controls, investigate potential risk factors for vitamin D deficiency in people with intellectual disabilities and assess available treatments.

Cross-sectional observational study followed by treatment evaluation.

Almost twice as many patients with intellectual disabilities had vitamin D deficiency (25(OH)D <50 nmol/l) compared with controls (77.3% v. 39.6%, P<0.0001). In the intellectual disabilities group, winter season (P<0.0001), dark skin pigmentation (P<0.0001), impaired mobility (P = 0.002) and obesity (P = 0.001) were independently associated with lower serum 25(OH)D. In most patients, 800 IU colecalciferol daily normalised 25(OH)D levels.

Vitamin D deficiency is highly prevalent in people with intellectual disabilities, partly because of insufficient exposure to sunlight. Screening and treatment strategies, aiming to reduce these patients' high fracture risk, should be introduced. Similar strategies may be required in other psychiatric populations at risk for fractures and with a tendency to spend excessive time indoors.

Mood instability is a common reason for psychiatric referral. Very little is known about how patients with unstable mood experience assessment and diagnosis.

To investigate the experiences of assessment and diagnosis among patients with mood instability and to suggest improvements to this process.

Qualitative study, gathering data through individual interviews with 28 people experiencing mood instability and receiving a psychiatric assessment in secondary care.

Participants described the importance of receiving an explanation for their symptoms; the value of a good interpersonal relationship with their clinician(s); being listened to and acknowledged; and being involved in and informed about clinical decisions. These needs were not, however, consistently met. Receiving a psychiatric diagnosis, including a diagnosis of bipolar disorder or borderline personality disorder, evoked both positive and negative responses among participants, relating to stigma, personal understanding and responsibility, prognosis and treatment.

Patients with mood instability seek explanation for their symptoms and difficulties, empathetic care and consistent support as much as cure. Clinicians may incorrectly assume what patients' attitudes towards diagnosis are, a mismatch which may hamper the development of a strong therapeutic relationship. Clear, patient-centred communication, which acknowledges the patient's experience, may result in greater patient engagement and satisfaction.

Despite frequent use, little is known about the metabolic and endocrine side-effects of antipsychotics in individuals with intellectual disability.

To compare indices of obesity, glucose, lipids and prolactin between antipsychotic-treated and antipsychotic-naive individuals with intellectual disability and also between participants with intellectual disability and controls from the general population.

Observational study comparing 138 antipsychotic-treated and 64 antipsychotic-naive participants with intellectual disability in one National Health Service trust with general population controls.

Antipsychotic treatment comprised: risperidone 48%, olanzapine 18%, thioxanthenes 10%, other 24%; monotherapy 95% of participants; mean treatment duration 8 years; median daily chlorpromazine equivalent dose 108mg (range 16–667). Metabolic indices were the same or more favourable in the intellectual disability group than the general population control group but overweight/obesity and type 2 diabetes were more prevalent in the women in the intellectual disability group than the control group. Metabolic indices were similar, statistically or clinically, between the antipsychotic-treated and the antipsychotic-naive groups but there was a non-significant trend towards a higher rate of type 2 diabetes in the antipsychotic group. A total of 100% and 70% of participants on amisulpride/sulpiride and risperidone respectively had hyperprolactinaemia, with secondary hypogonadism in 77% and 4% of affected women and men.

Antipsychotics, on average, did not increase metabolic risk, although the existence of a susceptible subgroup at risk of diabetes cannot be excluded. Some antipsychotics induced hyperprolactinaemic hypogonadism, requiring active management. However, our findings suggest that antipsychotics at the low doses routinely prescribed for people with intellectual disability are generally safe in relation to metabolic adverse effects, even if efficacy remains poorly defined.

Valproate is one of the most used mood stabilisers for bipolar disorder, although the evidence for the effectiveness of valproate is sparse.

To compare the effect of valproate v. lithium for treatment of bipolar disorder in clinical practice.

An observational cohort study with linkage of nationwide registers of all people with a diagnosis of bipolar disorder in psychiatric hospital settings who were prescribed valproate or lithium in Denmark during a period from 1995 to 2006.

A total of 4268 participants were included among whom 719 received valproate and 3549 received lithium subsequent to the diagnosis of bipolar disorder. The rate of switch/add on to the opposite drug (lithium or valproate), antidepressants, antipsychotics or anticonvulsants (other than valproate) was increased for valproate compared with lithium (hazard ratio (HR) = 1.86, 95% CI 1.59–2.16). The rate of psychiatric hospital admissions was increased for valproate v. lithium (HR = 1.33, 95% CI 1.18–1.48) and regardless of the type of episode leading to a hospital admission (depressive or manic/mixed). Similarly, for participants with a depressive index episode (HR = 1.87, 95% CI 1.40–2.48), a manic index episode (HR = 1.24, 95% CI 1.01–1.51) and a mixed index episode (HR = 1.44, 95% CI 1.04–2.01), the overall rate of hospital admissions was significantly increased for valproate compared with lithium.

In daily clinical practice, treatment with lithium seems in general to be superior to treatment with valproate.

Law 180 eliminated psychiatric hospitals for the care of people with chronic psychosis in Italy. After 30 years, we review the consequences for the practice of psychiatry in Italy and parallels for England and Wales. We argue that the substitution of legal/political direction for clinical leadership means psychiatrists may cease to merit the privileges and responsibilities of being doctors.