OBJECTIVE:To write clinical guidelines for the use of psychotropic drugs during pregnancy and breast-feeding for daily practice in psychiatry, obstetrics and paediatrics.METHOD:As we wanted a guideline with a high degree of consensus among health professionals treating pregnant women with a psychiatric disease, we asked the Danish Psychiatric Society, the Danish Society of Obstetrics and Gynecology, the Danish Paediatric Society and the Danish Society of Clinical Pharmacology to appoint members for the working group. A comprehensive review of the literature was hereafter conducted.RESULTS:Sertraline and citalopram are first-line treatment among selective serotonin reuptake inhibitor for depression. It is recommended to use lithium for bipolar disorders if an overall assessment finds an indication for mood-stabilizing treatment during pregnancy. Lamotrigine can be used. Valproate and carbamazepin are contraindicated. Olanzapine, risperidone, quetiapine and clozapine can be used for bipolar disorders and schizophrenia.CONCLUSION:It is important that health professionals treating fertile women with a psychiatric disease discuss whether psychotropic drugs are needed during pregnancy and how it has to be administered.
Because bipolar disorder was thought to occur in discrete episodes, it was generally considered reasonable to discharge patients into the care of their general practitioner (GP) ‘between’ episodes. However, it has become apparent that a considerable degree (up to 90% in a given year) of ongoing disability and residual symptoms are present between episodes 1. Patients with bipolar disorder may change symptom status an average of six times a year and polarity more than three times annually 2. Therefore, brief contact with services only during the symptomatic phase is not optimal, and relapse prevention through psychoeducation, family work or cognitive behavioural therapy (CBT) may best be done in a dedicated service 3. The development of bipolar clinics in the UK has been slow, in part because government statements of priority for mental-health services, such as the National Service Framework (NSF) 4, did not address treatment provisions for bipolar disorder. The most recent update of the NSF 5 only addressed the National Institute for Health and Clinical Excellence (NICE) review of medications for bipolar disorder, underscoring the impetus given to rethinking bipolar service provision after the recent development and approval of several new medications. Psychiatric care for patients with bipolar disorder has typically involved out-patient appointments with a psychiatrist and long-term medication, with increased support or admission to hospital at times of relapse. In recent years, there have been changes in both the role of the psychiatrist 6 and organisation of psychiatric services aiming to reduce out-patient load and workload of consultants by favouring the transfer of patients back to primary care. Unfortunately, primary- and secondary-care services are often not equipped to treat patients with mood disorders, who require long-term care and complex medication regimens. The ideal setting to treat patients at all stages of their illness is in specialised units that operate within an existing trust and are composed of trained clinicians who understand the natural course of the disease. Typically, up to 70% of patients referred to bipolar clinics with a diagnosis of treatment-resistant unipolar major depression have been misdiagnosed and are in fact bipolar 7. The advantage of dedicated bipolar clinics compared with traditional models of care is the provision of correct diagnoses within a clinical setting along with the prescription of appropriate medication through improved knowledge of available and emerging treatment options; promotion of a longer duration of stability, through awareness of early warning signs and rapid response to early signs of relapse, as well as improved patient knowledge; adherence to a care plan; improved patient skills for managing illness; maintenance of cognitive functions; and implementation of a proven 21-week expert bipolar psychoeducation group 8. Altogether, these benefits contribute to improved treatment outcomes and inadvertently minimise the numerous risk factors that could potentially lead to suicide 1. In maximising treatment outcomes for the patient, it is vital to ensure continuous support from the clinical staff, including training to identify recurring symptoms, strategies to self-monitor illness progression (i.e. with the help of a diary, mood or life chart) 9 and the availability of emergency contact numbers to ensure a partnership that works towards a mutually agreed treatment regimen. A well-established and trusting doctor–patient alliance in bipolar disorder may be an important predictive factor in determining treatment adherence. Patient perception of a clinician's support of their autonomy has also been shown to positively influence adherence, and patient satisfaction with their service provider has been shown to predict a better attitude towards their illness. Together with joint decision-making on treatment, the consistency of meeting with a dedicated clinician should help patients to engage with their therapy and view it as a long-term and collaborative commitment 10. The role of bipolar clinics may help reduce the risk of ongoing functional impairment in all domains of life including work, relationships, physical health and substance misuse, lack of which are associated with a prolonged lack of continuous specialist care. Only half of patients with bipolar disorder are able to report early warning signs or prodromes 11; therefore, therapeutic interventions and psychoeducation for patients with bipolar disorder can only be approached outside of acute episodes when the patient is able to gain insight into their illness and learn about therapeutic opportunities and treatment options. Bipolar clinics provide a controlled and experienced environment wherein patients and caregivers can be educated about bipolar disorder to gain insight into the illness. In addition, bipolar clinics can improve society's understanding of bipolar disorder and contribute to finding opportunities for patient reintegration into society, to strive for an independent lifestyle. Moreover, a continued clinic–patient relationship can help patients with bipolar disorder overcome barriers they might encounter when returning to work 12. Therapeutic strategies that optimise community-based management and prevent recurrence and hospitalisation have been shown to reduce the economic burden of illness and improve patient quality of life 13. Psychoeducation is a cost-effective intervention for patients with bipolar disorder compared with standard care that results in a reduction in secondary-care costs, such as hospitalisation, and that has been incorporated successfully into the regular operations of many bipolar clinics throughout Europe. Psychoeducation in combination with pharmacotherapy aids patients in maintaining a controlled lifestyle, allowing them to contribute to society by maintaining their employment status between episodes, which has been shown to improve treatment outcomes and patient morale 14. The set-up of a bipolar clinic requires a number of considerations, outlined in Fig. 1, before going into operation. The first consideration is whether the clinic will be established as a separate entity from existing National Health Service (NHS) services with independent sponsorship, a dedicated group of healthcare professionals including psychiatrists, nurses, psychologists and pharmacists; or as an integrated service within existing NHS services. Second, the role of the clinic must be established beforehand (i.e. early diagnosis, relapse prevention programmes, medical education, medical therapy or disorder management), as it will dictate the degree of specialist care required to provide adequate care for patients with bipolar disorder. The clinic could also provide additional specialist services, such as crisis teams, alcohol and substance abuse treatment, and physical health monitoring, which are common issues in patients with bipolar disorder. A further aspect to consider is the appropriate patient referral scheme (i.e. intake from primary vs. secondary care), which will determine who is responsible for initial patient assessments and how patient discharge planning and follow-up are going to be conducted. Once the role of a bipolar clinic is established, a number of key organisational issues, such as required staff levels, operation of the bipolar clinic in parallel to existing services and patient availability, must be considered. Critical decisions include whether the clinic assumes an advisory role only, with generic services remaining responsible for the case management, or whether the clinic takes over case management 24 h a day, 7 days a week vs. a 9–5-week day setting, supported by out-of-hours services. In addition, some fundamental parameters need to be guaranteed to ensure patient benefit and mental-healthcare professional satisfaction. Regular training is essential to all staff involved in a bipolar clinic. In particular, consultants unfamiliar with the concepts of psychoeducation may require preparation to ensure optimal delivery of psychoeducation in addition to standard care. A clear understanding of roles and responsibilities within a bipolar clinical team, and between a clinic and existing services, is essential to offset preconceptions that bipolar clinics increase staff workload instead of decreasing it. Potential problems regarding clinic staff workload, stress levels and patient treatment continuity can be managed through nurse-led teams, onsite medical cover and community team members as front-line staff that includes social workers and bipolar disorder specialists as part of the initial diagnosis and assessment team. One important challenge for bipolar clinics is the reintegration of patients into non-bipolar clinic services after psychoeducation. Consultants not involved in the running of a bipolar clinic may see them as a competitor service and could be less likely to take on patients released from a bipolar clinic. A goal of psychoeducation is to inform the patient on a variety of topics regarding bipolar disorder ranging from symptom awareness to medication, thus providing a basis for the patient to be actively involved in the decision-making process regarding treatment and available care programmes. However, with patients with bipolar disorder, it can be difficult to judge whether they are ready to take on those responsibilities, and it might be difficult for a consultant to accept that the patient wants to influence their treatment plan and has the knowledge and insight to do so. The typical NHS bipolar clinic should be modelled after the Barcelona Bipolar Clinic 15. Services should be provided during a day-long session, once per week with additional sessions and evening group psychoeducation on alternative days. The main objectives of bipolar clinics, as stipulated in the Barcelona model, are outlined in Table 1. In addition to risk factors and early warning signs, bipolar clinics should emphasise the need for regular physical health screening 16 associated with both bipolar disorder and its pharmacological management 17. Bipolar clinics should aim for an open and honest relationship between clinic users and staff, giving realistic but accessible expectations of access and encourage patients to provide feedback on their experience with the clinic's services, including location, timing, and accessibility for public transport and parking. The clinic's objectives should involve users in treatment planning: in the case of group psychoeducation, the mode of session delivery and the choice of whether to involve family members 9, 15 and the wider community. In addition to standard measures of outcome, the central goals of the service from first episode onwards should include functionality related improvements such as quality of life, social activities, work life and opportunities for reintegration into society. The bipolar clinic should encourage carers and families to participate in psychoeducation sessions separate to those attended by patients. Through workshops and practical sessions, bipolar clinics should educate their staff, local health organisations and commissioning bodies that good expert care reduces the burden of bipolar disorder on health services through the reduction of relapse rates. An essential part is a close working relationship with early intervention services to identify and treat comorbidities common to bipolar disorder, such as substance misuse, alcohol misuse, personality disorders and attention deficit hyperactivity disorder (ADHD) 18, and to avoid missed diagnoses. Specific themes to be emphasised in the treatment rationale of a bipolar clinic are as follows: i) the efficacy and limitations of monotherapy with mood stabilisers, such as valproate or lithium, and their safety and tolerability profiles in patients with bipolar disorder, especially in women of childbearing age; ii) the efficacy and safety of combination therapy with atypical antipsychotics and traditional mood stabilisers; and iii) the nature, duration and efficacy benefits of psychoeducation for patients with bipolar disorder. Clinical staff are encouraged to improve their expertise in the previously mentioned areas by keeping abreast of current expert literature, both original research and meta-analyses, and training in the chosen model of psychoeducation. Upon patient referral to the bipolar clinic, a thorough and structured interview should be conducted to outline a detailed psychiatric and treatment history, followed by physical health screening and appropriate medical tests. Subsequently, the patient's psychiatric status should be evaluated using standard rating instruments, such as the Mood Disorder Questionnaire (MDQ), the Hamilton Depression Rating Scale, the Young Mania Rating Scale and the Beck's Depression Rating Scale. At first visit, patients may be seen by a nurse consultant and a junior doctor, followed by a multidisciplinary review and an additional clinical interview with medical and nursing consultants, who may initially follow up on the patient 2–4 times per week. NHS bipolar clinics may provide CBT, family sessions and psychoeducational and general support sessions depending on patients’ needs, and regularly liaise with community mental-health teams (CMHTs), psychological therapy and non-psychiatric services. The major point of continued patient contact should be a nurse consultant, who is supported by a crisis team, duty doctors, wards and non-psychiatric services to provide assistance during practice hours and out-of-hours. The average time of a patient stay in a bipolar clinic is 6–24 months; however, this time frame may increase owing to the complexity of psychological or physical comorbidities, or the complexity of drug regimes. Following treatment in a bipolar clinic, patients should be referred to the recovery service for ongoing care within CMHTs, with indefinite continued support and advice from the bipolar clinic. The patient is a woman in her mid-20s working as a chef. She is talented and enjoys her work, but frequently comes into conflict with other staff members and is either fired or resigns, regularly displaying characteristics of mild violence. She usually finds alternative employment quickly, but becomes bored easily, which on occasion is cause for dismissal. The patient has a history of drug (LSD and amphetamine) and excessive alcohol use, which caused conflict with the police for drunk and disorderly conduct and possession of drugs (cannabis and cocaine). She is homosexual and has had several monogamous relationships. She has a partner of 3 years and is planning marriage. The patient has had periods of moderately severe depression, lasting for days or weeks, but there is a reactive element, in which the depression may have resulted from an unexpected setback at work or a relationship conflict. The patient is very petite (barely seven stone [44 kg] in weight) and has had problems with eating disorders. She attempted suicide by overdosing several times, as well as having had episodes of arm slashing in the previous 10 years. She has a family history of mood disorder and had been sexually abused by a male relative during childhood. Her medical history (including worsening with antidepressants), her answers to the MDQ and a more detailed family history suggested a diagnosis of bipolar disorder. She has participated in CBT and dialectical behaviour therapy with no clear benefit and often has failed to attend sessions. The patient reported that counselling sessions addressing her childhood abuse were unhelpful. She has been given a past diagnosis of emotionally unstable personality disorder, borderline subtype, with additional codes for ADHD and gender role disturbance, and was referred to a bipolar clinic for an opinion on diagnosis and treatment. The patient has had previous frequent contact with mental-health services, mainly following overdose or arm-slashing episodes. She has had some brief admission ward stays in hospital; however, she has neither found the contact helpful nor was willing to engage with ongoing services. The patient has been prescribed numerous antidepressants, antipsychotics and benzodiazepines in the past, but does not regard them as effective. Occasionally, her symptoms would worsen when using antidepressants, increasing her argumentativeness and irritability. Antipsychotics lead to sedation without noticeable impact on symptoms such as second-person hallucinations. Discussions of possible treatments were complicated by her avoidance of any treatment that might result in weight gain. After attending and completing all the psychoeducation group sessions, treatment with lithium was initiated. This treatment regimen was supplemented with aripiprazole or occasionally with quetiapine upon exceptional sleep disturbances. Upon emergence of symptoms such as depression and a feeling of worthlessness, she participated in 1–4 CBT sessions without her partner. Treatment with lithium and psychoeducation resulted in a moderation of alcohol intake and lack of consumption of drugs and antidepressants. Post-lithium symptom stability was enhanced, and conflicts at work and with the authorities were almost absent throughout 2 years of monitoring. Where implemented, NHS bipolar clinics have been a success locally and with specialisation of function trust-wide. Bipolar clinics may treat patients with related mood disorders, but their focus should be towards patients with bipolar disorder and to raise awareness of bipolar clinics as treatment facilities that uphold the best interest of the patient, their families and the community. As such, bipolar clinics provide support in optimising treatment and minimising drug interactions and toxicity, support working to a mutually agreed care plan, help to maintain employment and relationship networks, educate patients and their carers, and efficiently coordinate and manage complex care. Evidence shows that few patients treated in bipolar clinics drop out, and service provision can be made maximally accessible within local resource constraints. Even in the current climate of the UK's NHS budgetary constraints, it is possible to set up bipolar clinics within the context of existing NHS services. Resources can often be provided with some extra training and minor rearrangement of existing services. The workshop on which this supplement is based on was supported by Bristol-Myers Squibb, Uxbridge, UK. Editorial support for the preparation of this manuscript was provided by Ogilvy Healthworld Medical Education, London, UK; funding was provided by Bristol-Myers Squibb. The case study presented in this manuscript does not represent an individual patient, but is a collation of characteristics typical for patients with bipolar disorder. This manuscript is a result of a 1-day educational standalone symposium sponsored with an unconditional educational grant by Bristol-Myers Squibb, who also sponsored this publication. Professor Allan H. Young is employed by Imperial College London. He is an Honorary Consultant Psychiatrist with WLMHT (NHS UK); has given paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders; has no share holdings in pharmaceutical companies; was a Lead Investigator for the Embolden Study (AstraZeneca); BCI Neuroplasticity study and Aripiprazole Mania Study; and for investigator-initiated studies from AstraZeneca, Eli Lilly and Wyeth. He has received grant funding (past and present) from: NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); and is co-holder of one European patent for the use of glucocorticoid antagonists in the treatment of depression. Professor Anthony Hale is employed by Kent & Medway Partnership NHS Trust and King's College London. He has given paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders, schizophrenia, attention deficit hypersensitivity disorder and post-traumatic stress disorder. He has no share holdings in pharmaceutical companies. He is Principal Investigator for the Oasis study (DSRU for AstraZeneca) and for two pivotal agomelatine studies for Servier, as well as studies for Lilly, Lundbeck, Janssen and BMS.
OBJECTIVE:This article reviews the characteristics of bipolar disorder and approaches to minimise physical health risks, as well as treatment options, and their influence on patient quality of life (QoL).METHOD:The content of this article is based on the proceedings of a 1-day standalone symposium in November 2011 exploring how to establish a bipolar clinic within the context of existing services in the UK's National Health Service.RESULTS:Bipolar disorder is a common mental disorder and often under-recognised in patients with major depressive episodes. Patients are largely dependent on family and carers to lead normal lifestyles and have difficulties maintaining relationships. Mental health and physical health are closely linked, with risk factors such as weight gain, metabolic syndrome, smoking and diabetes contributing to cardiovascular disease and early death. Antipsychotics may induce treatment-related comorbidities, thus further contributing to a low QoL of patients. Symptoms of comorbidity or depression are frequently relieved through self-medication and substance abuse, thus increasing patient health and suicide risk. Therefore, regular health monitoring and patient education in risk factor minimisation are required.CONCLUSION:Early pharmacotherapeutic and psychoeducational interventions are required to improve treatment outcomes, as well as improving patient understanding of ways to minimise comorbidity development.
OBJECTIVE:Disturbances in circadian rhythms have been associated with major depression and may be an underlying mechanism for the disorder. Resynchronisation of circadian rhythms may provide a new approach to treatment, especially by manipulating melatonin secretion. Melatonin is secreted at night and is a stable marker of circadian rhythms. The timing of its secretion can be changed by exogenous melatonin, agonism of specific melatonin receptors in the suprachiasmatic nucleus, its suppression by light and by sleep deprivation.METHOD:As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128 (Suppl. 444): 2-15; and 'Getting depression clinical practice guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013;128 (Suppl. 444): 24-30.] addressing chronobiology, in this article, we conducted a selective review of studies that have examined the antidepressant effects of exogenous melatonin, light therapy, sleep deprivation and melatonin receptor agonists.RESULTS:Antidepressant effects were identified for bright light therapy, especially for seasonal affective disorder; sleep deprivation, although its antidepressant effect is time limited; and for the novel antidepressant agomelatine with agonistic properties for the MT1 and MT2 receptors and antagonism of 5HT2c receptor. The role of melatonin as an antidepressant has yet to be demonstrated.CONCLUSION:Shifting the circadian secretion of melatonin using the strategies reviewed offers a new approach to treating depression.
OBJECTIVE:As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013;128(Suppl. 444):2-15; and 'It's time we managed depression: The emerging role of chronobiology' Malhi et al. Acta Psychiatr Scand 2013;128(Suppl. 444):1] examining chronobiology in the context of depression, this article examines recent western clinical practice guidelines (CPGs) for the treatment of depression with respect to the recommendations they make, in particular as regards chronobiological treatments, and briefly considers the implications of their methodology and approach.METHOD:Five international treatment guidelines, which had been published in the past 5 years, were identified, representing North American and European views. Chosen guidelines were reviewed by the authors, and the relevant recommendations were distributed for discussion and subsequent synthesis.RESULTS:Most current guidelines do not address chronobiology in detail. Chronotherapeutic recommendations are tentative, although agomelatine is considered as an option for major depression and bright light therapy for seasonal affective disorder. Sleep deprivation is not routinely recommended.CONCLUSION:Recommendations are limited by the lack of reliable therapeutic markers for chronotherapeutics. Current evidence supports use of light therapy in seasonal depression, but in non-seasonal depression there is insufficient evidence to support reliance on chronotherapeutics over existing treatment modalities.
