Mood disorders are common, with over 7% of men and 10% of women suffering from a mood disorder during their adult life.¹

The original unipolar-bipolar dichotomy, has become blurred with recent data pointing to broader forms of bipolar spectrum disorder.² It is thought that almost 1% of the population suffer from bipolar I disorder characterised by periods of mania interspersed with longer periods of syndromal or sub-syndromal depression.¹

Bipolar II disorder has also been well characterised (though it lacks randomised controlled treatment trials), by long intractable periods of depression interspersed with brief hypomanic or mixed episodes.² Bipolar II disorder has a higher prevalence (2-3%), a later onset and a higher prevalence in women (Female: Male 2:1) than bipolar I disorder.²

Angst and others, have described more subtle forms of bipolar disorder, under bipolar spectrum disorder with short-lived hypomanias, subsyndromal or rapid cycling clinical courses and hyperthymic or cyclothymic temperaments.²

Misdiagnosis

Approximately 15-20% of established cases of bipolar spectrum disorders are misdiagnosed as having unipolar depression.¹ Though few randomised controlled treatment trials of bipolar II or bipolar spectrum disorder have been published, bipolar spectrum disorders are important to recognise in terms of treatment and prognosis. For example, bipolar II disorder has a worse long-term prognosis than unipolar depression, is less responsive to conventional antidepressants, and a lower threshold for mood stabilisers is often indicated.²

It is also well recognised that bipolar I disorder with psychosis is on a spectrum with schizophrenia and schizoaffective disorder.¹ At least 20% of patients with psychotic mania will describe at least one diagnostic Schneiderian first rank symptom suggestive of schizophrenia.¹ Additionally, mood incongruent delusions, particularly persecutory, are common in mania or psychotic depression. Modern diagnostic approaches specify a diagnosis of bipolar I disorder when psychotic symptoms, however bizarre, only occur with mood symptoms of mania or depression, whereas for a diagnosis of schizophreniform psychosis (<6 months duration), schizophrenia (>6 months duration) or schizoaffective disorder, psychosis must occur at some time in the course of illness in the absence of mood symptoms.³ Much emphasis is laid on the presence of negative symptoms of schizophrenia such as avolition, apathy, restricted affect and poor self-care later in course, but more subtle neuropsychological deficits in attention, concentration and executive functioning are observed with bipolar I disorder even when patients are well. Such deficits may worsen over time, particularly in those who have had many manic episodes.¹

Late-onset mania

First manic episodes in late-life (>65 years) are relatively uncommon – about 5% of all new-onset bipolar disorder cases.^1,4 Organic disorders should be ruled out in all new-onset cases in late-life, particularly delirium, due to drug or alcohol withdrawal and infection, in acute hospital settings, as behavioural disinhibition, insomnia, overactivity, paranoia and restlessness are often present in delirium, although patients are usually confused with obvious cognitive deficits. Similarly, disinhibition or apathy are often present in frontotemporal dementias and depression is often the earliest manifestation of subcortical dementias.¹

Early-onset mania

Early-onset mania and rapid cycling mood disorder can be hard to distinguish from personality disorder, particularly cluster B personality disorders such as emotionally unstable, histrionic and narcissistic subtypes as well as hyperthymic and cyclothymic personalities. Co-morbidity of bipolar I disorder with personality disorder is common, with a life-long co-morbidity of about 60%, with a similar co-morbidity of bipolar II disorder, with cluster C disorders particularly dependant and avoidant subtypes.⁵

To overcome diagnostic uncertainty a comprehensive collateral history is important and as thorough a history as possible in terms of course and precipitants, and to evaluate whether personality difficulties appear to predate onset of manic episode. It is important assess consistency of symptoms over time and avoid prescribing mood stabilisers, which may lead to lifelong treatment and have significant risks in terms of weight gain, contraception and teratogenicity, until a clear cut diagnosis is established. Finally, the majority of patients with bipolar disorder will have another  co-morbid axis I psychiatric disorder, with over 50% having a life-long prevalence of alcohol or substance misuse and over 40% having a co-morbid anxiety disorder, particularly social anxiety, which often predates onset of bipolar disorder.⁵

Mania and hypomania

Historically, definitions of mania and hypomania were confused even among psychiatrists and my experience as a trainee changed with every consultant supervisor ranging from hospitalised patients being called hypomanic to outpatients with a slightly disturbed sleep pattern being described as manic! In practice, diagnosis should be relatively straightforward. 

The US Diagnostic and Statistical Manual IV (DSM-IV) defines hypomania as being in an expansive, irritable or elated mood for at least four days and having at least three of the following seven symptoms; elevated self-esteem, reduced need for sleep, increased talkativeness, flight of ideas or racing thoughts, distractibility, increased goal-directed activity, increased pleasurable activities with potentially harmful consequences such as overspending or sexual indiscretions. These symptoms should be observable to others and may affect functioning though not severely in terms of occupation, relationships or social functioning.³ If psychotic symptoms, or a severe disruption in functioning or hospitalisation occurs, criteria for mania are fulfilled.³ Somewhat confusingly, the definition specifies elevated or irritable mood for at least a week to fulfil criteria for mania which seems to lack validation from a research or clinical perspective. 

The International Classification of Diseases 10 (ICD-10) criteria do not specify a duration of symptoms but mainly distinguish between mania and hypomania by severity of impaired social, occupational and relationship functioning in addition to psychotic symptoms and hospitalisation.⁶

Distinguishing between mania and hypomania has become more important with the recognition of different and more subtle subtypes of mood disorder which impacts on treatment and prognosis. The safest distinction, which is in accordance with the main diagnostic systems, would be to define any period of elated or irritable mood lasting a few days with significant disruption in functioning, or hospitalisation or psychosis as mania.

Does psychotherapy work for bipolar disorder?

Given the high risk of recurrence (>95%) and burden of long-term symptomatology (>50% follow-up time) it is important to evaluate whether non-pharmacological therapies improve outcome.⁷ Over the last decade, randomised controlled trials from Colum’s and Vieta’s research in Barcelona have proved conclusively that group psychoeducational approaches reduce relapse in bipolar disorder over five-year follow-up compared to treatment as usual.⁸

These group psychoeducational approaches focus on adherence to treatment, education about illness and self-help and are typically conducted weekly for six-months when patients are euthymic for a period of time.⁸ Additionally, multiple psychoeducational sessions for families of patients have also been shown to prevent relapse.⁹ Such long-term psychoeducational approaches for bipolar disorder have not been introduced in an Irish setting although St Patrick’s University Hospital runs 12-week day-patient psychoeducational groups for bipolar disorder for those with health insurance.

Given that the typical patient with bipolar disorder is taking a median of five to seven medications and that estimated non-compliance is between 30-50% with partial compliance being even higher, it is not surprising that trials of treatment adherence have also prevented recurrence in bipolar disorder.¹⁰

Cognitive behavioural therapy

Outcome of randomised controlled trials for cognitive behavioural therapy (CBT) in bipolar disorder have been more equivocal.¹¹ In contrast to excellent rationales and outcomes for anxiety disorders and unipolar depression, cognitive therapy for bipolar disorder lacks a unifying theory, with treatment manuals overlapping with psychoeducational approaches focusing on awareness of symptoms, lifestyle regulation (circadian rhythms and life-events), medication adherence and relapse prevention (triggers and prodromal symptoms).

Small randomised controlled trials and meta-analyses showed some benefits from CBT, especially early in course of illness. However, the largest naturalistic randomised controlled trial of CBT in bipolar disorder failed to find a benefit in main outcome measures compared to treatment as usual.¹¹

This naturalistic Medical Research Council sponsored study enrolled 254 subjects in four provincial cities and one university town in the UK and included patients with axis I and II co-morbidity.¹¹ Patients in this study had been diagnosed with bipolar disorder an average of 17 years earlier and were not currently unwell but had experienced an episode within the previous year.¹¹ Patients received 20 sessions of CBT over six months, with two booster sessions afterwards or treatment as usual and showed no differences on any of the main outcome measures such as recurrence or re-hospitalisations over 18-month follow-up.¹¹ However, on further analysis, patients with six or less prior episodes who had CBT were significantly less likely to suffer recurrence whereas those with 12 or more prior episodes, especially of mania, were more likely to recur if they received CBT.¹¹ CBT appeared to be beneficial for those early in their course of illness and detrimental to those later in course of illness or who had several previous episodes of mania. 

Recent neuropsychological studies have shown that patients with bipolar disorder develop deficits in attention, concentration and executive function even when euthymic for a considerable time and that deficits worsen with number of episodes particularly of mania.¹ The poorer outcome with CBT late in course of illness may relate to established neuropsychological deficits which make patients less amenable to psychological therapies. In summary, psychological approaches, particularly group psychoeducation with patients and families, adherence therapy and CBT, have important roles to play in those with bipolar disorder but should be mainly focused on those early in course of illness.  

Is cannabis abuse associated with bipolar disorder?

Acute, short-lived, cannabis induced psychotic and manic episodes have been long recognised. However, the role of cannabis in the development of enduring psychotic illness has emerged over the past decade. Cohort studies, particularly of male conscripts, have shown that regular cannabis use during mid-teens increases risk of developing early-onset schizophrenia by 1.5-2 fold among men.¹²

Similarly, urban areas such as south London have seen an explosion in incidence of schizophrenia among young men in recent years, which is likely to be associated with regular use of cannabis among young African and African-Caribbean men.¹³ For example, studies using the epidemiological case register in Camberwell in south London, where about 15-20% are regular users of cannabis, have shown a doubling of incidence and an earlier age at onset of schizophrenia over the past 35 years.¹³ Data relating incidence of bipolar disorder to cannabis use are more equivocal. The incidence of bipolar disorder in Camberwell has increased significantly over the same time period but much less than for schizophrenia and may be accounted for by the psychosocial effects of effects of migration rather than cannabis use.¹⁴ Interestingly, data are emerging showing that men in areas where cannabis use is common develop bipolar disorder four to five years earlier than women suggesting that cannabis may be a factor in earlier onset of disorder.^14.15

Furthermore, regular cannabis use affects compliance with prescribed medications, psychosocial function and risk of recurrence.^14,15  Regular early cannabis use is associated with an increased incidence of psychosis and is likely to be associated with an earlier onset of bipolar disorder and poorer long-term outcome particularly for young men. 

Case Report 1

A 74-year old retired solicitor was admitted for assessment of hypomania following GP with a six-month history of behavioural change. He had become disinhibited and flirtatious towards younger women he encountered shopping or walking. His family noticed that he had been spending more on clothes and furniture as well as in property when previously he had been very frugal. He was more cheerful, talkative and anecdotal having been a serious introverted man all his life. He had always been interested in horseracing but began to go to race meetings several times a week and gambled more. He needed less sleep and his language had become coarser and more circumstantial recently.

On admission he was grandiose constantly referring to important people he had met in his career. He had high levels of energy, pressure of speech and flight of ideas. He was repetitive in speech, had word finding difficulties and difficulty in remembering names and directions in hospital. On further collateral history his daughter had felt that her father had seemed depressed over the last 10-years since the death of his wife and more socially withdrawn but had been able to practice as a solicitor until his early seventies. He had been prescribed low dose antidepressants, namely venlafaxine, a SNRI, for about 5 years and was taking an ACE inhibitor for hypertension. They had been worried about his memory as he was more forgetful losing his train of thought regularly and not recognizing his son on one occasion.

A diagnosis of bipolar affective disorder, current episode hypomania (ICD-10 F31.0) was made but given his disinhibition and memory difficulties an organic cause such as dementia was considered. Routine bloods including a dementia screen and physical investigations were normal. Antidepressants were stopped due to hypomania and lithium was commenced and titrated to 600mgs nocte with weekly blood tests settling at 0.6 mmol/l. His mood settled  during his six-week inpatient stay and speech became much less rapid. Mini-Mental State Examination was undertaken weekly during his stay and was normal at between 27-29/30. To further evaluate cognitive functioning he underwent the Addenbrooke’s Cognitive Examination Revised (ACE-R)¹⁶ which scored 86/100, 90% specific for dementia. MRI brain showed ischaemic change and frontotemporal atrophy. He was seen by occupational therapy (OT) to improve social routines and was referred by hospital social workers to community services. Diagnoses of bipolar disorder and early dementia were discussed with the patient and his family and he was referred to community old-age psychiatry services, for driving assessment and for regular follow-up neuropsychology investigations.

Discussion  

The peak incidence of bipolar disorder in the late teens and early twenties with a second peak in mid-life, though new presentations of mania in late-life are not uncommon, 5% after 65 years.⁴ Late-onset mania is often related to organic illness which can present with symptoms that resemble mania or “unmask” or exacerbate pre-existing bipolar disorder.¹ Delirium, secondary to acute medical illness, can present with symptoms suggestive of mania in a hospital setting and subcortical dementias often present first with mood symptomatology. Medications such as steroids can induce manic episodes particularly in those susceptible to mood disorder. Finally, frontotemporal dementias can present with apathy or avolition suggesting depression or behavioural change, disinhibition and impaired executive functioning suggestive of mania.

In this case, symptoms of depression appear to have predated changes in memory or cognition which may suggest an underlying affective disorder but the onset of hypomanic symptoms came on at same time as memory disturbance. It is difficult to know whether the hypomanic symptoms and behavioural changes were due to organic change or whether these were co-morbid disorders. It was decided to treat symptomatically with lithium while investigating the memory disorder in more depth. Symptoms of mania improved on lithium which is considered to be neuroprotective, as did memory and executive functioning to a lesser extent.

Mini-Mental State Examination (MMSE) is a simple bedside test for dementia, in the absence of delirium, with a score of 21 or less being very suggestive though in this case, the normal MMSE is likely to reflect high educational attainments and IQ, though he showed impairment in the more comprehensive and sensitive ACE-R. Other simple bedside tests which aid diagnosis include proverbs and similarities which test abstract reasoning, verbal fluency and trail making tests which test executive functioning and digit span which tests concentration and immediate memory.

Case Report 2

A 31-year old single man was voluntarily admitted with persecutory delusions that people in his town were following him to kill or torture him. He described passivity phenomena, namely that people were able to communicate with him through their minds, and thought insertion, where he felt that people could insert negative and paranoid thoughts into his brain. He denied hallucinations but was obviously depressed with a low mood for 4 months, impaired energy to work, lack of interest in usual activities such as fishing and music, sleep and appetite disturbance, futility feelings and impaired libido. He described a period of elation on holidays in Cyprus 2 years earlier where he became elated and irritable with grandiose ideas about having special powers associated with reduced need to sleep and very high levels of energy. This episode culminated in a 10-day admission to another Hospital where his symptoms were attributed to “lack of sleep, excessive alcohol and use of cannabis and ecstasy”.

He had used cannabis recreationally for five years but use had escalated over the past year with agitation and craving on cessation. He felt paranoid for nine months though not to delusional intensity. He described a strong family history of both unipolar depression and bipolar disorder. A full organic work-up including MRI Brain was normal and he was diagnosed with bipolar disorder. An antipsychotic, olanzapine was titrated to a dose of 10 mgs/day with amitriptyline 125 mgs/nocte for depression. He attended a   dual-diagnosis psychoeducational programme for substance misuse as his symptoms improved. He was discharged after two months much improved though still with residual symptoms of depression.

Within four months of discharge he again began to exhibit symptoms of psychosis, with persecutory delusions, and depression despite being abstinent from cannabis and alcohol and was unable to return to work. He gained 10 kgs in weight on olanzapine and was readmitted.  Olanzapine was changed to sulpiride, an antipsychotic with less risk of weight gain and lamotrigine, a mood stabilizer with antidepressant effects was added. As well as attending a mood-disorder psychoeducational programme he had 12 sessions of individual cognitive behavioural therapy (CBTp) for psychosis and social anxiety with good effect. He was discharged after several weekends at home where he engaged in exposure therapy around people whom he had previously feared. He has subsequently remained well for 3 years and returned to full functioning with OPD and CBT treatment.     

Discussion

Until recently, psychiatrists help a relatively benign view about the psychoactive properties of cannabis. It was recognised that cannabis could induce a short-lived florid “drug induced psychosis” that was usually self-limiting. However, compelling data, particularly from cohort studies have shown that regular use of cannabis during teenage years is likely to increase risk of an enduring psychotic disorder.¹² Similarly, south London, where recreational cannabis use is common, has seen a doubling in the incidence of psychosis over the last 30 years in contrast to other urban areas where incidence of psychosis has fallen.¹³ Early cannabis use is also likely to lead to an earlier age at onset for psychosis and bipolar disorder which may account in large part for the earlier onset of bipolar disorder among men compared to women in south London.¹⁴ It appears likely that regular early cannabis use can increase risk of developing an enduring psychotic illness particularly in those who are genetically susceptible such as the above case.

Regarding treatment, he clearly benefited from a dual-diagnosis programme for substance misuse which led to abstinence from cannabis and should be considered in patients with dual diagnosis especially considering the effect of psychoactive drugs on psychosis. Additionally, he benefited from individual cognitive behavioural therapy for psychosis (CBTp) which aims at improving insight and understanding of psychotic phenomena as well as functional outcome and through exposure to situations he was avoiding.¹⁷ CBTp has been shown to be effective in randomized controlled trials at preventing relapse and improving outcome particularly alongside antipsychotic treatment.¹⁷ Finally, he gained significant weight on olanzapine. Young men are at a particular risk of significant weight gain on olanzapine as well as other atypical antipsychotics. It is advisable, given the long-term health implications, that when significant weight gain occurs to consider an atypical antipsychotic with less risk of weight gain such as aripiprazole or risperidone, a mesolimbic selective antipsychotic such as sulpiride or amisulpiride or a high potency typical antipsychotic at low dose such as haloperidol.      

Case Report 3

A 21-year old single Nigerian dental student was admitted voluntarily from a city centre police station where he had been arrested after causing a public disturbance. He presented with a two-week history of psychotic symptoms. On admission he described passivity phenomena feeling that people on the television could direct him, he described third person auditory hallucinations about a voice he felt was communicating God's will. He described persecutory delusions about fellow students and lecturers trying to harm him. He also described grandiose delusions about being “special” and having a message to save the world. He had obvious pressure of speech and flight of ideas with loose connection between thoughts. After admission he became angry and aggressive towards fellow patients when they questioned his beliefs and was transferred to a more acute ward. Investigations including MRI brain were normal and a diagnosis of schizophreniform psychosis was made given his first rank symptoms including passivity phenomena and third person auditory hallucinations. Olanzapine was commenced which he responded well to and he was discharged within three weeks.

Within two months of discharge he began to exhibit symptoms of depression with a persistent low mood, total social withdrawal and avoidance of college. He lost interest in sports and described sleep disturbance and an impaired libido. Venlafaxine XL was titrated to 225 mgs/day for depression with good effect. However, within six weeks of starting venlafaxine he exhibited psychotic symptoms mainly grandiose delusions about being “special” and “chosen” by God. He developed pressure of speech and persecutory delusions. He was readmitted to hospital where antidepressants were stopped and a diagnosis of bipolar I disorder was considered. He was commenced on lithium and valproate chrono as mood stabilizers with antimanic effects and doses were titrated rapidly. He improved rapidly in hospital and was discharged within four weeks. He has remained well as an outpatient on maintenance mood stabilizers for three years with short-lived subsyndromal depressive episodes.    

Discussion

Diagnosis of bipolar I disorder is often mis-diagnosed as schizophrenia or schizophreniform psychosis when patients are assessed acutely with florid and bizarre psychotic symptoms especially first-rank symptoms such as passivity phenomena, thought echo or third person auditory hallucinations.¹ At least 20% of patients during an episode of psychotic mania will describe first symptoms of schizophrenia.¹ Bipolar African-American and African-Caribbean patients are more likely to present with acute florid psychotic symptoms during manic episodes and studies show they are more likely to have a mis-diagnosis of schizophrenia or schizoaffective disorder.¹⁸ Furthermore, African and African-Caribbean patients are more likely to present with mania at their first clinical presentation with bipolar disorder than Caucasians and the clinical course may be different over time.¹⁹ In contrast to Caucasian patients who spend much more time with depressive symptoms than mania,  studies from Nigeria have shown that multiple manic episodes are the predominant course which may account for the better outcomes among African-American and African-Caribbean populations as lengthy depressive episodes are more likely to affect employment and social functioning long-term.²⁰ These differences in clinical course and outcome are likely to have implications for treatment for bipolar disorder as most randomized trials to date have been carried out on Caucasian samples. Finally, as in this case, pathways to care are often different for patients of an ethnic minority. In the UK AESOP study African and African-Caribbean patients with psychosis were less likely to have accessed a GP and were more likely to be admitted involuntarily and through the police suggesting much less early engagement with primary or psychiatric health care services.^21,22      

References

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