Carvalho - review article bipolar disorder
● Presence of manic/hypomanic episodes that may alternate with depressive episodes
● overconfidence, grandiosity, talkativeness, extreme disinhibition, irritability, decreased
need for sleep, and highly elevated mood
● Psychotic symptoms such as delusions and hallucinations occur in up to 75% of manic
episodes
● Bipolar I : manic episodes
● Bipolar II : hypomanic episodes
● The presence of at least one hypomanic episode in a life trajectory is considered to be
consistent with the diagnosis of bipolar II disorder
● Cyclothymic disorder is characterized by recurrent depressive and hypomanic states,
lasting for at least 2 years, that do not meet the diagnostic threshold for a major affective
episode
● DSM : symptoms must be present for 1 week for a diagnosis of a manic episode or 2
weeks for diagnosis of depressive episode
● Onset : 20 years
● An earlier onset is often associated with a poorer prognosis, longer treatment delays,
more severe depressive episodes, and higher prevalences of concurrent anxiety and
substance use disorders
● First episode usually depressive - misclassified as major depressive disorder
● In a ⅓ of affected persons not diagnosed until 10 years after onset
Epidemiology and burden
● Lifetime prevalence 2.4%
● 12 month prevalence 1.5%
● Prevalence varies by country
● Bipolar I M=W
● Bipolar II W>M
● Tentative associations between IBS, childhood adversity and bipolar disorder
● Cognitive and psychosocial dysfunction during acute episode
● 6-7% commit suicide
● High rates of comorbid disorders
○ Anxiety
○ Substance use
○ Personality disorder
○ Adhd
● Metabolic syndrome, migraine, obesity, type 2 diabetes more common
● Twice the risk of death (suicide/medical condition)
,Genetic and neurobiological features
● Common variants of genetic risk only account for 25% of heritability
● Gene-environment interaction
● Kindling hypothesis : first episode due to stressor, subsequent episodes can occur
without exposure to stressor
● Poorly characterized epigenetic mechanisms contribute to kindling phenomenon
● Progressive changes in brain structure → reduced cortical thickness in pfc, pathways
subserving neuroplasticity, inflammation, increase in stress
● Deregulation of mitochondrial function
● Aberrations in HPA AXIS → Pathophysiology and progression of bipolar disorder
● Neuroprogression → worsening of cognitive and functional impairments
● Prevalence of type 2 diabetes higher in people with multi episode bipolar
● As bipolar illness progresses, the response to mood stabilizing medications may
decrease
, Management
● Primary care practice improve mental and physical health outcomes
● Medical and psychiatric conditions that mimic affective episodes should be ruled out
during diagnostic assessment
● Selection of initial treatment : patient’s preference, coexisting medical and psychiatric
conditions, previous responses to treatment
● During acute affective episodes the safety of the patient should be ensured
● Evidence based pharmacologic interventions
Treatment of acute episodes
● Acute mania
○ Antipsychotic agents/mood stabilizers
○ If there is no response to a medication after ½ weeks a different medication may
be considered
○ Antipsychotic + mood stabilizer for severe mania
○ In children risperidone > lithium
○ A lot of metabolic adverse depression
○ Haloperidol, paliperidone
○ Electroconvulsive therapy
● Acute depression
○ A low initial dose with gradual upward dose adjustment
○ Combination therapies = antipsychotics and mood stabilizers
○ Rct :ketamine
○ Affective switches - treatment with antidepressants may carry a risk of switches
to hypomania/mania + accelerated cycling between them
○ Second generation antidepressants (SSRIs) may be effective for short term
management of bipolar disorder
○ Risk of mania switches higher in Bipolar I patients → antidepressants avoided
○ Ect effective for patients with treatment resistant and multitherapy resistant
bipolar depression
○ Psychoeducation, cbt, family focused therapy, DBT, MBCT, ITP, social rhythm
therapy
○ children/adolescents : family education + CBT
● Maintenance treatment
○ Combination of pharmacologic, psychological and lifestyle interventions
○ Ideally maintenance treatment started shortly after onset of illness
○ Lithium monotherapy more effective in preventing manic and depressive
episodes
■ Side effects : renal failure, hypothyroidism, polydipsia, tremors, increase
in parathyroid hormone levels
○ Meta Analysis : lithium, antipsychotics may reduce long term morbidity in juvenile
bd
○ Side effects
○ Divalproex - teratogen → not recommended for women of childbearing age
○ Maintenance ect
● Presence of manic/hypomanic episodes that may alternate with depressive episodes
● overconfidence, grandiosity, talkativeness, extreme disinhibition, irritability, decreased
need for sleep, and highly elevated mood
● Psychotic symptoms such as delusions and hallucinations occur in up to 75% of manic
episodes
● Bipolar I : manic episodes
● Bipolar II : hypomanic episodes
● The presence of at least one hypomanic episode in a life trajectory is considered to be
consistent with the diagnosis of bipolar II disorder
● Cyclothymic disorder is characterized by recurrent depressive and hypomanic states,
lasting for at least 2 years, that do not meet the diagnostic threshold for a major affective
episode
● DSM : symptoms must be present for 1 week for a diagnosis of a manic episode or 2
weeks for diagnosis of depressive episode
● Onset : 20 years
● An earlier onset is often associated with a poorer prognosis, longer treatment delays,
more severe depressive episodes, and higher prevalences of concurrent anxiety and
substance use disorders
● First episode usually depressive - misclassified as major depressive disorder
● In a ⅓ of affected persons not diagnosed until 10 years after onset
Epidemiology and burden
● Lifetime prevalence 2.4%
● 12 month prevalence 1.5%
● Prevalence varies by country
● Bipolar I M=W
● Bipolar II W>M
● Tentative associations between IBS, childhood adversity and bipolar disorder
● Cognitive and psychosocial dysfunction during acute episode
● 6-7% commit suicide
● High rates of comorbid disorders
○ Anxiety
○ Substance use
○ Personality disorder
○ Adhd
● Metabolic syndrome, migraine, obesity, type 2 diabetes more common
● Twice the risk of death (suicide/medical condition)
,Genetic and neurobiological features
● Common variants of genetic risk only account for 25% of heritability
● Gene-environment interaction
● Kindling hypothesis : first episode due to stressor, subsequent episodes can occur
without exposure to stressor
● Poorly characterized epigenetic mechanisms contribute to kindling phenomenon
● Progressive changes in brain structure → reduced cortical thickness in pfc, pathways
subserving neuroplasticity, inflammation, increase in stress
● Deregulation of mitochondrial function
● Aberrations in HPA AXIS → Pathophysiology and progression of bipolar disorder
● Neuroprogression → worsening of cognitive and functional impairments
● Prevalence of type 2 diabetes higher in people with multi episode bipolar
● As bipolar illness progresses, the response to mood stabilizing medications may
decrease
, Management
● Primary care practice improve mental and physical health outcomes
● Medical and psychiatric conditions that mimic affective episodes should be ruled out
during diagnostic assessment
● Selection of initial treatment : patient’s preference, coexisting medical and psychiatric
conditions, previous responses to treatment
● During acute affective episodes the safety of the patient should be ensured
● Evidence based pharmacologic interventions
Treatment of acute episodes
● Acute mania
○ Antipsychotic agents/mood stabilizers
○ If there is no response to a medication after ½ weeks a different medication may
be considered
○ Antipsychotic + mood stabilizer for severe mania
○ In children risperidone > lithium
○ A lot of metabolic adverse depression
○ Haloperidol, paliperidone
○ Electroconvulsive therapy
● Acute depression
○ A low initial dose with gradual upward dose adjustment
○ Combination therapies = antipsychotics and mood stabilizers
○ Rct :ketamine
○ Affective switches - treatment with antidepressants may carry a risk of switches
to hypomania/mania + accelerated cycling between them
○ Second generation antidepressants (SSRIs) may be effective for short term
management of bipolar disorder
○ Risk of mania switches higher in Bipolar I patients → antidepressants avoided
○ Ect effective for patients with treatment resistant and multitherapy resistant
bipolar depression
○ Psychoeducation, cbt, family focused therapy, DBT, MBCT, ITP, social rhythm
therapy
○ children/adolescents : family education + CBT
● Maintenance treatment
○ Combination of pharmacologic, psychological and lifestyle interventions
○ Ideally maintenance treatment started shortly after onset of illness
○ Lithium monotherapy more effective in preventing manic and depressive
episodes
■ Side effects : renal failure, hypothyroidism, polydipsia, tremors, increase
in parathyroid hormone levels
○ Meta Analysis : lithium, antipsychotics may reduce long term morbidity in juvenile
bd
○ Side effects
○ Divalproex - teratogen → not recommended for women of childbearing age
○ Maintenance ect
