Bipolar Disorders

• Bipolar Disorders are a group of mental disorders characterized by prolonged periods of excessive elevation in mood with/without depressive episodes. It can be considered as a group of disorders that bridge between the depressive and psychotic disorders.
  • Bipolar I Disorder
  • Bipolar II Disorder
  • Cyclothymic Disorder
  • Substance/Medication-Induced Bipolar and Related Disorder
  • Bipolar and Related Disorder Due to Another Medical Condition
  • Other Specified Bipolar and Related Disorders

Epidemiology

• The lifetime prevalence for bipolar I disorder is approximately 0.6%, with equal gender distribution.
• Bipolar I disorder is more common in
  • high income (1.4%) than low income (0.7%) countries
  • Separated, divorced, or widowed individuals have higher rates of bipolar I disorder.
• mania more common in men, more depressive episodes in women 
• onset from childhood 5-6 yo to 50yo, average age of 30yo 

Onset

• For many people, their first episode was triggered by a major life stressor.
• Subsequent episodes have also been linked with a stressful life event.
• no specific personality traits are associated with bipolar 
• most often starts with depression (70%) and is a recurring disorder
• most will suffer both depressive & manic episodes (although some only have manic episodes)
• manic episodes often have rapid onset (hours/days) but evolves over few weeks
  • an untreated manic episode lasts about 3 months (so continue Rx for at least 3/12) 
  • 90% who have a manic episode are expected to have another 
  • Need to Dx & Tx early with antipsychotics +/- BZ initially then with mood stabilisers (Li, carbamazepine, valproate) as prognosis worsens with repeated episodes
  • After about 5 episodes, the interepisode interval stabilises to about 6-9 months
• 15% of pts with bipolar have > 4 episodes per year 🡺 ‘rapid cyclers’ 

Prognosis

• Bipolar has poorer prognosis cf MDD
• lithium prophylaxis improves the course & prognosis but only 50-60% respond well
• Between 6 to 7% of individuals will die by suicide, and suicide is a significant cause of bipolar disorder mortality
• poor prognostic factors:
  • bad premorbid occupational status
  • alcohol & substance abuse
  • psychotic features
  • depressive features
  • interepisode depressive features
  • male gender
• good prognostic factors:
  • short duration of manic episodes
  • advanced age at onset
  • fewer suicidal thoughts
  • lack of comorbid ψ or medical problems 
• 7% do NOT have a recurrence of Sx
• 45% have more than 1 episode
• 40% have chronic disorder (most people have about 10 manic episodes in their life)
  

COURSE & PROGNOSIS:

• mood disorders have chronic relapsing courses
• once they have had 1^st episode (precipitated by stressors) they are more at risk of 2^nd episode 

With DDx, always think:

• primary psychiatric condition (SZ, MDD, bipolar, GAD, etc) 
• secondary psychiatric condition (eg depression secondary to dementia) 
• secondary to general medical condition (GMC) 
• secondary to substance-use 
• organic cause
• depressive phase:
  • same DDx as for depressive disorder above
• manic phase:
  • bipolar I
  • bipolar II
  • cyclothymic disorder
  • mood disorder from general medical condition or substance-induced 
  • consider borderline / narcissistic / histrionic / anti-social personality disorders
  • schizophrenia
    • merriment, elation & infectiousness of mood favour mania 
    • manic mood, rapid or pressured speech & hyperactivity favour mania 
    • onset of mania is often rapid & perceived as a marked sudden change from previous behaviour
• catatonic phase:
  • can be depressive phase of bipolar I or catatonic schizophrenia 
• medical conditions – a large variety of medical/neurological conditions & substances can produce similar Sx. In particular, antidepressants can also precipitate mania in some patients! (look at temporal relationship).  

Bipolar I Disorder 

• disorder in which at least one manic episode has occurred 
• if manic symptoms lead to hospitalization, or if there are psychotic symptoms, the diagnosis is bipolar I 
• commonly accompanied by at least 1 MDE but not required for diagnosis 
• time spent in mood episodes: 53% asymptomatic, 32% depressed, 9% cycling/mixed, 6% hypo/ manic 

Bipolar II Disorder 

• disorder in which there is at least 1 MDE, 1 hypomanic episode, and no manic episodes 
• while hypomania is less severe than mania, bipolar II is not a “milder” form of bipolar I 
• time spent in mood episodes: 46% asymptomatic, 50% depressed, 1% cycling/mixed, 2% hypo/ manic 
• bipolar II is often missed due to the severity and chronicity of depressive episodes and low rates o spontaneous reporting and recognition of hypomanic episodes 

MANIC EPISODE 

• abnormally and persistently elevated/expansive/ irritable mood   +
• abnormally and persistently increased goal-directed activity or energy 
• lasting ≥1 wk and present most of the day, nearly every day
• ≥3 of the following symptoms:
  • D – distractibility (attention too easily drawn to irrelevant external stimuli)
  • I – indiscretion & ↑ participation in pleasurable activities with painful consequences (unrestrained shopping sprees, sexual indiscretions, or foolish business investments)
  • G – grandiosity & ↑ self-esteem
  • F – flight of ideas or subjective experience that thoughts are racing
  • A – activity ↑ goal-directed (socially, work, school, sexually) or ψ-motor agitation 
  • S – sleep need perceived as ↓
  • T – talkativeness & pressure to keep talking 

• marked impairment in social or occupational functioning or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features 

Hypomanic Episode 

• abnormally and persistently elevated/expansive/ irritable mood   +
• abnormally and persistently increased goal-directed activity or energy 
• lasting ≥4 days and present most of the day, nearly every day
• ≥3 of the following symptoms:
  • D – distractibility (attention too easily drawn to irrelevant external stimuli)
  • I – indiscretion & ↑ participation in pleasurable activities with painful consequences (unrestrained shopping sprees, sexual indiscretions, or foolish business investments)
  • G – grandiosity & ↑ self-esteem
  • F – flight of ideas or subjective experience that thoughts are racing
  • A – activity ↑ goal-directed (socially, work, school, sexually) or ψ-motor agitation 
  • S – sleep need perceived as ↓
  • T – talkativeness & pressure to keep talking 
• uncharacteristic change in functioning that is observable by others 
• but not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization  
• absence of psychotic features (if these are present the episode is, by definition, manic) 

Mixed Features 

• an episode specifier in mania or depression that indicates the presence of both depressive and manic symptoms concurrently, classified by the disorder and primary mood episode component (i.e. BD, current episode manic, with mixed features) 
• clinical importance due to increased suicide risk and appropriate treatment 
• if found in patient diagnosed with major depression, high index of suspicion for BD 
• while meeting the full criteria for a MDE, the patient has on most days ≥3 of criteria B for a manic episode 
• while meeting the full criteria for a manic/hypomanic episode, the patient has on most days ≥3 of criteria A for a depressive episode (the following criterion A cannot count: psychomotor agitation, insomnia, difficulties concentrating, or weight changes)

DEPRESSIVE EPISODES:

• depressed mood & anhedonia (inability to experience pleasure) are key Sx of depression 
• pt’s may say that they feel blue, hopeless, down in the dumps or worthless 
• 2/3 of depressed pts contemplate suicide & 10-15% commit suicide (roughly same for SZ) 
• Once they’ve had a past attempt at suicide, they now have the strongest risk factor for future attempts 
• Anxiety is a common Sx of depression & affects 90% of depressed patients
• Alcohol abuse & somatic Sx (constipation/headaches) often complicate the Tx of depression 
• Diurnal variation is common (50%) where ↑↑↑ severity in morning & better at night  

• CHILDREN:
  • Sx can include: school phobia, excessive clinging to parents, poor academic performance, substance abuse, anti-social behaviour, sexual promiscuity, truancy & itinerancy 
• ELDERLY:
  • More common than in general population (which is 15-25% women) so prevalence in elderly ranges from 25-50% 
  • Often correlated with low SES, loss of spouse, concurrent physical illness & social isolation 
  • Often underdiagnosed & undertreated (perhaps because of ageism accepting it as ‘normal’ for them or also because they present with more somatic complaints)

Mental state Exam	Depression	Mania
Appearance & Behaviour:	generalised psychomotor retardation is the most common Sx (although ψ-motor agitation is seen, esp. in elderly 🡪 agitation is seen as hang wringing & hair pulling) stooped posture, no spontaneous movements downcast or averted gaze, avoiding eye-contact (can appear similar to the psychomotor retardation seen in catatonic schizophrenia) – thus DSM-IV-TR has mood disorders ‘with catatonic features’	Excited, talkative, sometimes amusing & frequently hyperactive Can be grossly psychotic & disorganised & require physical restraints +/- IM sedatives
Speech:	↓ rate, abnormal rhythm, ↓ volume (R/R/V) Respond with single-word answers + delayed response to questions (sometimes minutes!!)	↑↑ rate, rhythm, ↑ volume (R/R/V) Often cannot be interrupted when speaking (very intrusive & rude)  Speech is often disturbed & at ↑↑ mania, they can get loosening of associations (derailment), flight of ideas, word salad & neologisms  Can be totally incoherent & like that of a person with schizophrenia
Affect, Mood & Feelings:	Depressed mood is the main Sx (50% will deny depressive feelings & don’t particularly appear depressed) Family members/ employers often bring in or send them in because of social withdrawal & generalised decreased activity	Euphoric Can be irritable (esp. if plans not going their way)  Low frustration tolerance 🡪 anger & hostility  Emotionally labile 🡪 can switch from laughter to irritability to depression in mins/hours
Thought:	negative view of world & of themselves non-delusional thoughts about loss, guilt, suicide & death  10% have thought disorder of stream/production 🡪 thought blocking & profound poverty of content	↑ self esteem & self-aggrandisement (grandiose) Easily distracted & unrestrained + accelerated flow of ideas  Delusions occur in 75% of manic pts 🡪 great wealth, special abilities or power
Perception:	if they have delusions/hallucinations 🡺 MDD + psychotic features if grossly regressed – mute, not bathing, soiling 🡺 MDD + catatonic features delusions & hallucinations that are consistent with depressed mood are ‘mood congruent’ mood-congruent delusions include: guilt, sinfulness, worthlessness, poverty, failure, persecution & terminal somatic illnesses (eg cancer & ‘rotting brain’) mood-incongruent delusions involve grandiosity – exaggerated power, knowledge & worth (eg belief that they are being persecuted for being the Messiah	Can get bizarre & mood-incongruent delusions & hallucinations in mania
Judgement & Insight	judgement best assessed by reviewing pt’s actions in recent past & behaviour during interview depressed patient’s insight is often excessive 🡪 overemphasis of Sx, their disorder & life problems  can be difficult convincing them that improvement is possible	Impaired judgement is the hallmark of mania pts They may break laws about credit cards, sexual activities & finances (can result in financial ruin!)  Very little insight into their disorder (can abuse Dr for trying to stabilise their mood & remove euphoria)
Rapport/ Reliability/ Risk	can be difficult establishing rapport reliability has to be questioned 🡪 can be overly negative about previous response to antidepressants trialled  risk & safety – to self & to others (broadly – includes children who may be neglected, elderly, etc), suicidality, homicidality, etc)	Notoriously unreliable in information supplied Lying & deceit are common 🡪 collateral Hx!
Cognition & Sensorium	orientation – most are orientated to time, person & place (T/P/P) but sometimes they don’t have the energy or will to answer 50-75% will have cognitive impairment (depressive pseudo-dementia) – pts complain of ↓ concentration & memory	Minor cognitive deficit (due to diffuse cortical dysfunction)  Gross orientation & memory are intact (but can be so euphoric that they answer incorrectly)

Treatment

• biological
• monotherapy with antidepressants should be avoided
• Mood stabilizers vary in their ability to “treat” (reduce symptoms acutely) or “stabilize” (prevent relapse and recurrence) manic and depressive symptoms; multi-agent therapy is common
  • treating mania:
    • lithium, divalproex, carbamazepine (2nd line), SGA, ECT, benzodiazepines (for acute agitation)
  • preventing mania:
    • same as above but usually at lower dosages, minus ECT and benzodiazepines
  • treating depression:
    • lithium, lurasidone, quetiapine, lamotrigine, antidepressants (only with mood stabilizer), ECT
  • preventing depression:
    • same as above plus aripiprazole, divalproex (note: quetiapine first line in treating bipolar II depression)
  • mixed episode or rapid cycling: multi-agent therapy: lithium or divalproex + SGA (lurasidone, aripiprazole)

Mood Stabilising Drugs

• Examples: Lithium, some antiepileptic drugs (Carbamazepine, Valproate, Gabapentin)
• Used prophylactically in bipolar depression
• Prevent swings of mood → ↓depressive and manic phases
• Require 3-4 wks to become effective
• In acute attacks → useful in ↓mania ONLY

Lithium

• Pharmacokinetics
  • ½ life: ~ 12hrs 
  • takes 2wks to remove from system
• Recommendations for monitoring patients on lithium
  • Lithium plasma level : 3-6 months
  • Renal function (eGFR) : Baseline then every 3-6 months
  • Thyroid function (TFTs) : Baseline then every 6-12 months
  • Calcium : Baseline then annually
  • Weight : Baseline then annually
• Adverse effects:
  • Cardiovascular effects: Sinus node dysfunction, ECG changes
  • Cognitive effects: Memory impairment
  • Dermatological effects: Psoriasis, acne, dry skin, alopecia
  • Endocrine/metabolic effects
    • Hypothyroidism
      • Reported prevalence rates of goitre are 4% to 51% and hypothyroidism is increased about six-fold.
      • In middleaged women, the risk of hypothyroidism may be up to 20%.
      • Goitre is thought to be due to the inhibitory effects of lithium causing increased TSH concentrations.
      • Hypothyroidism is easily treated with thyroxine.
      • Thyroid function test results usually return to normal when lithium is discontinued.
    • hypercalcaemia
    • weight gain
  • Gastrointestinal effects
    • Nausea
    • diarrhoea
    • dry mouth
    • metallic taste
  • Haematological effects: leucocytosis
  • Nervous system effects: Tremor, fatigue, muscle weakness
  • Renal and Urinary effects: Polyuria, polydipsia, nephrogenic diabetes insipidus, renal impairment
  • Peripheral oedema
• Acute toxicity
  • Toxicity reliably occurs when the serum lithium concentration is > 1.5 mmol/L, although it can
  • sometimes develop when the level is within the therapeutic range.
  • A patient’s lithium concentration may increase, for example, because of co-prescription
  • of a drug which reduces lithium excretion (most commonly an NSAID or thiazide diuretic) or because of simple dehydration.
  • Risk factors for toxicity when serum lithium levels are in the therapeutic range include a high starting dose, concomitant antipsychotic drug therapy, pre-existing EEG abnormalities, undetected cerebral pathology and genetic susceptibility
  • Neurological effects: confusion & motor impairment → coma, convulsions & death

Carbamazepine

• MOA: prevents repetitive firing of action potentials in depolarised neurones through blockade of Na⁺ channels

Sodium Valproate

• MOA: potentiates GABA
• Mood stabilising action relates to effects on protein kinase C

Gabapentin

• MOA: unknown
• Structurally related to GABA

Medication follow-up

• Medication trials should be monitored every 1-2 wks for up to 6 wks, when effectiveness of the medication can be properly assessed
• Is successful → continue meds for 6-12 months and then slowly tapering is considered
• Tapering of medications should be done gradually

None Pharmacological advice

1. psychological:
   • supportive psychotherapy
   • CBT
   • IPT
   • interpersonal social rhythm therapy
   • family therapy
2. social:
   • vocational rehabilitation
   • consider leave of absence from school/work
   • assess capacity to manage finances
   • drug and EtOH cessation
   • social skills training
   • recruitment & education of family members
3. Medication Management:
   • Take prescribed medications regularly as directed.
4. Maintain a Routine:
   • Establish and stick to a daily routine that includes regular sleep, meals, and exercise.
   • Disruptions to routine can sometimes trigger mood episodes.
5. Sleep Hygiene:
   • Ensure you get adequate and consistent sleep each night.
   • Lack of sleep can be a significant factor in triggering mood episodes.
6. Stress Management:
   • Develop healthy coping mechanisms for managing stress, such as mindfulness, meditation, or relaxation techniques.
   • Identify and avoid triggers that may contribute to stress.
7. Early Warning Signs:
   • Early warning signs:
     • increased activity, decreased need for sleep, and elevated mood, OR depressed mood, loss of energy, loss of interest in people or activities, impaired concentration
   • Keep a mood journal to track changes in mood, energy levels, and sleep patterns.
8. Emergency Plan:
   • Develop a crisis or emergency plan
   • Clearly outline steps to take in case of a potential relapse.
     • visit to the doctor when you
     • ask a friend to keep your credit card when you have the urge to shop for shoes
     • request that a relative drop by to visit when patient stop calling them, etc
     • ask friends and family to say specific things to you to highlight the possibility that becoming unwell