Bipolar affective disorder (previously termed manic depressive illness) is a common, severe and recurrent mental disorder that is marked by waxing and waning of affective (mood) symptoms as well as impairment in functioning, even during well intervals. Approximately 1-2.4% of the world’s population is affected, resulting in a significant disease burden and substantial years lost to disability.¹ While initial descriptions of the phenomenology and even pathophysiology of what we now know as bipolar disorder attempted to differentiate severe mental illnesses from those with a deteriorating course (ie. schizophrenia and related psychoses) to those with a periodic course (the mood disorders including bipolar illness), and additionally to regard depression and bipolar disorder as separate entities, some authorities now see considerable continuity between recurrent depressive and bipolar disorders along a broader spectrum of mood disturbance. 

Diagnosis

For a diagnosis to be made, there must be at least one episode of mania or hypomania (a milder, shorter duration version of mania) and at least one depressive episode. Accurate delineation of the approximate subtype of bipolar illness is an important aspect of understanding and correctly managing the condition and may have important treatment and prognostic implications. Although a single unitary cause remains elusive, it has long been appreciated that bipolar illness is among the ‘most genetic’ of all psychiatric illnesses, with up to 80% of patients having at least one close family member with some form of recurrent mood disorder or another. Successful rehabilitation from bipolar illness starts when patients come to understand that their symptoms are not psychological mirages, hiding deep tragic secrets or self-induced emotional injuries, but are indicators of a serious and real illness that requires prolonged and specific treatments. Delaying these interventions can increase the risk of suicide, increase the severity of illness, reduce the length of time between episodes, and even damage brain structures and neural connections.²

Bipolar mood disorder in context

The onset of the condition is primarily during young adulthood with equal distribution of prevalence between males and females. As many as 50% will be diagnosed before their 20th birthday, but there may be an additional peak around 45-54 years. Over 90% of people experiencing a single manic episode will have a recurrence of mood disturbance during their lifetime and up to 15% may die by suicide (as opposed to 10% of those with severe and recurrent unipolar depression), but additionally they have twice the standardised mortality rate of the population.³ Bipolar mood disorder is recognised as belonging to the World Health Organization’s top 10 list of illnesses that lead to disability and premature death. There is also a lifelong vulnerability to recurrence with considerable occurrence of co-morbidities, such as alcohol misuse and addiction (as part of self-medication) as well as overlapping with other psychiatric co-morbidities such as anxiety. It is estimated that 20 years after the onset of the condition, two-thirds of people experience disabling problems.⁴ The burden for family members and caregivers is also considerable with negative effects on close relationships and social activities, career potential and exercising financial responsibilities.  

Clinical assessment

The illness can be almost chameleon like in its presentation, with symptoms varying from one patient to the next and even from one episode to the next, within the same patient. The heterogeneity of presentations also make this one of the most difficult conditions to diagnose. More so than for other psychiatric disorders, the clinician needs to pay attention to the life history of the patient and to third party or collateral information from family and friends. A comprehensive assessment of anyone with suspected bipolar illness is essentially incomplete without this information. 

Classically periods of prolonged and profound depression alternate with periods of excessively elevated and/or irritable mood known as mania. Core symptoms of mania characteristically include a reduced need for sleep, pressurised speech, increased libido, reckless behaviour and impaired judgement, without regard for the consequences and in particular grandiosity. During severe episodes, there may be severe thought disorder and even psychotic symptoms. Hypomania implies a lesser degree of symptoms of mania and crucially less impairment and disability. Hypomania can even be perceived as a desirable state, with the patient subjectively feeling very well physically and mentally, but psychotic symptoms are not present and if the symptoms last for longer than a few days, then the line has most likely been crossed into a distinct manic state. As in mania, the basic symptom of the depressed phase of bipolar illness implies a change of mood in a negative direction. The prevailing mood is usually described as sad, unhappy, down or even just ‘depressed’. The common feature is that there is a dysphoric or unpleasant mood change. Some patients experience prominent anxiety rather than feeling down; others are very irritable. While the symptoms of low mood are very similar in bipolar and unipolar depression and differences are not consistent, people experiencing bipolar depression are more likely to experience excessive sleep and more lability of mood. They are also more subject to the emergence of psychotic symptoms and other common features are abrupt onset and sudden recovery. 

While the usual view of bipolar illness is of two extremes of mood – the highs and lows, which are seen as opposites – mixed states also occur and are the combination of manic and depressive symptoms at the same time. There may be significant loss of sleep but also a degree of agitation and distractibility and distressing overactivity. In practical terms a mixed state is important to detect, as the appropriate treatment differs in this phase of the illness, being more akin to treating a manic phase and responding preferentially to mood stabilising medication, as opposed to antidepressant treatments. 

Full assessment should consider:

Number of previous episodes (some of which may have been subclinical)

Average length of prior episodes

Average time between episodes and the degree of regained psychosocial functioning during recovery

Previous response to various treatments (especially treatment of early depressive episodes)

Family history of psychiatric difficulties

Current and previous use of alcohol and illicit substances. 

The degree of psychosocial support and interpersonal and community resources (or otherwise) enjoyed by the patient is crucial however in relation to the long-term prognosis of the condition. 

Classification

The main subtypes of the condition include the distinction between bipolar type 1 and type 2 and are well described in DSM-5.⁵ Bipolar type 1 is the most common form of the condition and its hallmark is a manic episode that lasts for at least a week – or any episode that requires a medical intervention. The majority of people (90%), but not all people, will also have periods of depression in this form of the illness. Untreated manic episodes will generally last three to six months, with depression persisting for six to 12 months without treatment. 

In bipolar type 2 the majority of individuals will experience hypomania rather than extreme mania and depression in this variant of bipolar illness can be protracted and severe. Important descriptors and riders that apply to bipolar types 1 and 2 alike are the presence of mixed features or co-occurrence of mania/hypomania and depression which may result in agitation, insomnia, significant changes in appetite, emergence of psychosis and, worryingly, suicidal thoughts. Another sequel to bipolar illness applying to both subtypes is the tendency towards rapid cycling or fluctuating between four or more depressive, manic or hypomanic episodes in a 12 month period. Rapid cycling affects around 10% of people with bipolar illness and may be associated with excessive deployment of antidepressants, as opposed to mood stabilisers in the condition. Lastly bipolar illness may follow a seasonal pattern whereby a person observes that each winter they may have a depressive episode, but their mania does not regularly follow a seasonal pattern. 

Cyclothymia, also known as bipolar type 3, presents with chronic mood disturbance of at least two years duration and the frequent hypomanic or depressive symptoms are less severe and are not classifiable as bipolar type 1, type 2 or unipolar depression. There is always the risk however that a person with cyclothymic symptoms may evolve or develop into a more prominent subtype of the condition, with emergent symptoms in keeping with either bipolar type 1 or 2. 

Bipolar type 4 is identified by manic or hypomanic episodes that manifest only after taking antidepressant medications and bipolar type 5 refers to patients who have a family history of bipolar disorder but who only have symptoms of major depression themselves.  

Several differentials should be considered in the context of suspected bipolar disorder, including schizophrenia. Delusions and hallucinations can occur in both conditions, but in bipolar disorder these are mood congruent so tend to be grandiose, while in schizophrenia they tend to be more bizarre and difficult to understand. Where features of schizophrenia and bipolar disorder are present in roughly equal proportion, a diagnosis of schizoaffective disorder should be considered. Frontal lobe pathologies can result in a loss of social inhibitions, which can also occur in mania or hypomania. Neurological investigation and imaging through CT or MRI can differentiate an organic cause from bipolar disorder. Emotionally unstable personality disorder (EUPD)/borderline personality disorder is characterised by affective instability which can present similarly to rapid cycling bipolar disorder. Mood changes tend to occur more rapidly in EUPD and other features of mania such as grandiose ideas or a marked increase in energy are generally not seen in EUPD. The effects of some illicit and prescribed medications such as steroids can cause a similar presentation to mania but this generally resolves as the implicated drugs wear off.  

Straightforward depression or not? Clues to underlying bipolarity

The question of whether a patient has major depressive disorder or bipolar disorder has been a persistent challenge in clinical practice and both research and anecdotal experience will tell us that bipolar disorder is not only confused with personality difficulties, substance misuse and schizophrenia, but also with depressive and anxiety disorders. A major challenge is to find the time to undertake a thorough history, to identify and explore any possible episodes of hypomania, which can change a diagnosis from a unipolar mood disorder (or major depressive disorder) to a bipolar subtype. Yet this must be done as there are direct treatment implications. 

It commonly takes up to a decade for many to get a diagnosis of bipolar illness (especially in the case of bipolar type 2). This is often because patients present in a depressed phase, don’t recall hypomania or mania, or because collateral history is not sought or is unavailable. It is not infrequent that for early onset depression a significant proportion (as many as 25% according to some experts) will ‘convert’ to bipolar illness during their lifetime. Symptoms can get ‘buried’ in drug or alcohol misuse and irritable mania may be harder to recognise. Certain features, especially in combination, are predictive of bipolar disorder however.⁶ These include broad indicators of bipolarity, none of which by themselves confirm a bipolar diagnosis but which should raise clinical suspicion in that direction.

Management

Management of bipolar disorder depends on the nature of the presenting episode and whether someone presents with acute mania or depression, as an acute episode of illness may necessitate an admission to inpatient care if there is a high risk of suicide or harmful behaviours due to impairment of judgement. Management of acute episodes is followed by a need to commence prophylactic treatment and engage and educate the patient to take responsibility for what will likely be a lifelong, but not necessarily a life-defining condition. Outpatient follow-up is crucial to enhance adherence with and scrutinise tolerability and effectiveness of treatment, monitor key parameters of wellbeing such as activity and sleep, and help the person build self management skills, identifying early signs of relapse and to build a support network and nominating spotters (trusted people who can objectively discern signs of relapse when individual insight is lacking). 

For acute mania, lithium is still offered as a firstline, long-term pharmacological treatment for bipolar disorder.⁷ Anticonvulsant mood stabilisers, namely sodium valproate and carbamazepine, may also be used as first-line mood stabilisers, either alone or in combination with lithium, for acute mania or mixed affective states, as can the antipsychotic mood stabilisers (risperidone, olanzapine, quetiapine and aripiprazole). Acute bipolar depression may be usefully treated by olanzapine, quetiapine or lamotrigine, which may also have a role in the management of rapid cycling mood disorder. Prophylactic mood stabilisers, which may be offered as monotherapy or in combination on a longer term basis, include lithium, sodium valproate, carbamazepine, lamotrigine or aripiprazole. 

Adjunctive medications can be useful for short periods as ‘rescue treatments’, eg. hypnotics, anxiolytics or low-dose antipsychotics for mixed episodes. Often anticipated and well understood side effects may preclude usage of some medications in certain populations, such as the concerns about the teratogenic potential of sodium valproate in younger women. Longer term deployment of mood stabilising medications is often required and abrupt discontinuation may lead to a rapid relapse but close monitoring of blood levels, in the case of lithium for example, can avert predictable side effects of hypothyroidism or renal impairment or weight gain in the case of other medications. Protocols are available which see patients being advised to take a single mood stabiliser, or two agents in combination with the subsequent addition of a low dose antipsychotic, depending on response to the first steps of initial treatment. Antidepressant medication may be necessary for the depressed phase of type 2 bipolar illness, but owing to the risk of switching into mania or induction of a rapid cycling state, the treatment duration should be relatively short (weeks and not months) with a policy to avoid potent agents such as serotonin-noradrenaline reuptake inhibitors (SNRIs).  

For some patients a specific psychotherapeutic intervention (in addition to usual psychiatric management and social support) will be needed. Approaches include psychodynamic, interpersonal, behavioural and cognitive therapies. In addition, couple, family and group therapy will be beneficial for some patients. The selection of such interventions is influenced by the local availability of such treatments, as well as patient needs and preferences. As most patients struggle with the impact of a chronic psychiatric illness, speak of a fear of recurrence and have residual interpersonal difficulties, support and education to teach acceptance of the illness and to develop support systems as well mood monitoring and early symptom detection is crucial.   

Latest updates and advances in treatment 

Recent pharmacological advances have been largely in the area of antipsychotic mood stabilisers, whether they include long-acting atypical injectable antipsychotics such as aripiprazole or risperidone, or the novel agent cariprazine, which may carry a lower risk of the metabolic syndrome. Longer term studies will be required to determine their long-term tolerability however.⁸

Genetic advances in mapping the specific genes associated with bipolar illness raise the prospect that precision medicine will be able to identify optimally targeted treatments and therapies based on analysis of a patient’s genetic profile. There is a greater understanding of how to avoid weight gain associated with many everyday treatments in bipolar illness, by use of agents such as metformin or topiramate to reverse rises in blood glucose and make treatment more sustainable. Transcranial magnetic stimulation is a non-invasive procedure that uses magnetic fields to simulate nerve cells in prefrontal cortical areas and is being studied as an alternative to ECT. Esketamine, administered intranasally, which is now licensed and available for treatment resistant depression may prove to have a role in bipolar depression also. Mindfulness-based cognitive behavioural therapy has a positive effect on regulating mood and easing depression and anxiety, and has been shown to reduce depressive relapses and, along with interpersonal and social rhythm therapy (specifically developed for people with bipolar disorder), is adding to the repertoire of evidenced based-therapies that complement psychoeducation and optimal self management of the illness. 

Avoiding chronicity and improving outcomes

Efforts to educate and develop high quality, diverse and multidisciplinary supports for people with the condition is the essence of restoring quality of life and long-term wellbeing to people with bipolar mood disorder. Improving adherence to treatment, minimising alcohol and illicit substance exposure, and collaborating with the patient about the choice of long-term treatment, and securing their buy in to adhere to this, is crucial. Seeing beyond the episode that is presented to the clinician and instead focusing on longer term stability of mood is key, when faced with difficult scenarios, such as severe bipolar depression. 

Potent or prolonged courses of antidepressant medications may be injudicious in the long run and lead to rapid cycling and manic switches; mood stabilising treatments may take longer to work but may be more effective. For primary care the crucial challenge is to not only monitor, but also to become familiar with treatments to treat bipolar illness, as the side effect burden associated with some medications is considerable. Collaboration between primary and secondary care to determine appropriate levels and optimal dose of many medications for each individual is critical, and the personal support network that patients are encouraged to create for themselves needs to be matched with a commitment from secondary and primary care to offer consistent and long-term support also.  

Conclusion

Although usefully seen as a spectrum of mood disorders, bipolar illness has core elements of mania, hypomania and depression. Comprehensive management means reducing stress and maladaptive coping, improving treatment adherence, relapse prevention, functional recovery and reducing medical co-morbidity. Having a collaborative, education-focused approach between patient, their supporter and the clinician or health professional will remain the cornerstone of effective longer-term treatment and care of these patients.