Bipolar Disorder: Symptoms & Risk Assessment

• Bipolar and related disorders are discussed in Human Behavior and Psychiatry PHA 535, during Spring 2025 with Dr. Levy.
• Instructional objectives include differentiating bipolar I, bipolar II, and cyclothymic disorders by applying DSM-5-TR diagnostic criteria and identifying core specifiers.
• Objectives also include formulating pharmacologic and non-pharmacologic treatment plans for bipolar-related disorders, and evaluating medication regimens, including laboratory results and side effects.

What is Bipolar Disorder (BPD)?

• Bipolar disorder is also known as manic-depression.
• It involves alternating cycles of depression and mania or their continuums.
• Severe episodes can be accompanied by hallucinations or delusions.
• Onset begins most commonly by ages 15-19, then second most common is at ages 20-24, although episodes can start as late as age 50.

What Causes Bipolar Disorder?

• Biochemical instability in the transmission of nerve impulses in the brain, involving multiple pathways, can cause bipolar.
• Bipolar disorder has a genetic component; first-degree relatives of a person with bipolar disorder are approximately 7 times more likely to develop it.
• Neuroinflammation theory is a potential cause of bipolar disorder.

BPD and Suicide

• Suicide risk is high in bipolar disorder.
• The mortality rate for those with BPD is 2-3x the general population.
• Risk factors include a history of previous suicide attempts, a history of rapid-cycling bipolar disorder, comorbid substance abuse, a mixed episode, and a current depressive episode.

BPD and Substance Abuse

• 61% of individuals with BPD have a lifetime history of any drug or alcohol use disorder.
• Detox ("drug wash out") is needed to distinguish between bipolar vs drug effects.
• Asking patients about drug use during each visit is crucial.

Bipolar I Characteristics

• Bipolar I involves a combination of mania and euphoric highs, often followed by severe depression or suicide.
• Mania without depression is rare.
• Diagnosis usually occurs after hospitalization, arrest, or family insistence.
• The first episode is often triggered by a stressful or changing life event.
• Such events involve beginning a new job, going to university, marriage, excessive stimulation, falling in love, starting a new project, staying out late and partying, vacation, or listening to loud/exciting music and video games.

BPD and Kindling

• Repeated electrical stimulation of the hippocampus in lab animals can lead to the development of a spontaneous seizure disorder, in which seizures occur without external stimulation.
• The earlier and more frequent the bipolar episodes, the more severe and persistent they become.
• The therapeutic goal is early, effective treatment.

Bipolar I Terminology

• A cycle is one entire rotation from each extreme of mania and depression (2 affective states or mixed).
• An affective episode is a manic or a depressive episode (or mixed).
• Cycles can be widely spaced or short with seemingly continual illness (rapid cyclers).
• Patients can have multiple depressive and/or manic states before having the opposite affective state; thus, there are more affective states than cycles.

DSM 5 TR Criteria for Manic Episodes

• Abnormally and persistently elevated or irritable mood lasting at least one week, or any duration if hospitalization is necessary.
• ≥ 3 manic symptoms must be present.
• Only one episode is needed for a diagnosis of Bipolar I disorder.
• Results in social or occupational dysfunction, requiring acute care.

Mania Features

The mnemonic DIG FAST is used to remember the features of mania

• D: Distractibility
• I: Impulsivity
• G: Grandiosity
• F: Flight of ideas
• A: Activity increase
• S: Sleep deficit
• T: Talkativeness
• Individuals experiencing mania may be preoccupied with political, personal, religious, and sexual themes.
• Impaired judgement leading to buying sprees, sexual indiscretions, and unwise business investments occur.
• Psychotic features, such as paranoia, delusions, and hallucinations, may be present, but are not a diagnostic necessity.

Bipolar II – Hypomania with Major Depression

• A less intense/milder form of mania.
• Some characteristics of mania, but "highs" do not interfere with a person's work or social life.
• No psychotic symptoms are present (if they are, it is mania, Bipolar I).
• Individuals can think they are fine when family and friends recognize the hypomania.
• May feel good.
• Patients often go off medication to induce a hypomanic episode.
• Can result in severe mania or can swing into suicidal depression.

Bipolar II DSM 5 TR Criteria

• Hypomanic Episode:
  • At least 4 continuous days of abnormally and persistently elevated or irritable mood.
  • ≥ 3 manic symptoms are present.
  • No significant social or occupational dysfunction.
• Has one or more major depressive episodes and at least one hypomanic episode.
• No history of mania or mixed episodes.
• Treated like Bipolar I.

Cyclothymic Disorder

• It is a milder form of BPD: "Bipolar light".
• In adults it must be present for 2 years, and 1 year in children and adolescents.
• There must be hypomanic symptoms.
• Persistent depressive disorder (dysthymia) is present with hypomanic symptoms that never meet hypomanic criteria.
• Individuals will not be symptom-free for longer than two months.
• Can progress to BPD I or II at any time.
• Individuals may be "Moody".

BPD I and II Core Specifiers

• Rapid Cycling
• Bipolar Disorder with Mixed Features
• Bipolar Disorder with Anxious Disorder
• Bipolar Disorder with Psychotic Features
  • Psychotic features are the only specifier that do not apply to cyclothymia.

BPD I/II/ Cyclothymia Rapid Cycling

• Four or more discrete affective episodes per year (either depressive or manic).
• Faster, and more often occurs with a shorter time period in between episodes.
• A longer duration and more refractory course is typical, “rapid relapsing"
• When diagnosing rapid cycling, the number of affective episodes, rather than cycles, is counted. Can also occur with hypomania and dysthymia
• Substance abuse (particularly cocaine) can mimic rapid cycling.
• About 50% of bipolar patients are affected.

BPD I/II/ Cyclothymia Rapid Cycling Risk Factors

• Risk factors include:
  • Women making up 80-95% of rapid-cycling patients
  • Treatment with antidepressants alone
  • Development of clinical or subclinical hypothyroidism (spontaneously or during lithium treatment)
• The combination of Lithium and lamotrigine (L and L) is superior to either one alone in treating sensitive rapid cycling bipolar.

BPD with mixed features

• Consists of a mixed hypomania-BD type I or II
• Mixed mania-BD type I
• A MDE (Major Depressive Episode) with mixed features-BD type I or II/MDD

BPD I/II/ Cyclothymia with Anxious Distress

• Must have ≥ 2 of the following symptoms for the majority of days during an episode:
  • Irritable, short-fused or "keyed up"
  • Restlessness
  • Difficulty concentrating due to worry
  • Feeling of dread/ impending doom
  • Fear of "loosing control"

BPD I/II with Psychotic Features

• Can occur during depressive or manic episodes
• Delusions: false beliefs that cannot be real
• Extreme paranoia
• Hallucinations: auditory, visual, tactile, olfactory, gustatory
• Catatonia
• A small percentage of patients

BPD and Related Disorders Differential Diagnosis

• Includes consideration of:
  • Delirium
  • Dementia
  • Substance-related disorders
  • Schizophrenia
  • Schizoaffective disorder
  • Delusional disorders
  • Factitious disorder
  • Malingering
  • Attention-deficit/hyperactivity disorder
  • Conduct disorder
  • Schizoid Personality Disorder (PD)
  • Borderline PD
  • Histrionic PD

Medications That Can Cause BPD Symptoms

• Isoniazid
• Procarbazine (cancer chemo)
• Decongestants
• Bronchodilators
• Procyclidine/ L-Dopa
• Street drugs/ Hallucinogens
• Benzodiazepines
• Corticosteroids
• Metoclopramide
• Cimetidine
• Sympathomimetic amines, including those for ADHD
• Disulfiram
• TCAS
• Caffeine/ Caffeinated sports drinks

Endocrine/Nutritional Causes of BPD Symptoms

• Hemodialysis
• Vitamin B12/folate deficiency
• Addison disease
• Hyper/hypothyroidism

Neurologic Causes of BPD Symptoms

• Multiple sclerosis
• Traumatic brain injury
• Seizure disorders
• Huntington disease
• Post stroke
• Benign/malignant brain neoplasms

Infectious Causes of BPD Symptoms

• Neurosyphilis
• Herpes simplex encephalitis
• HIV infection

BPD Treatment - Lifestyle, Therapies, and Medications

• Common BPD treatments include:
  • Benzodiazepines
  • Mood Stabilizers
  • Antipsychotics
  • Talk Therapy
  • ECT
  • Lifestyle changes

BPD & Lithium

• Lithium was the first medication developed to treat BP disorder, in the 1940s.
• Its mechanism of action (MOA) is unknown, but there are multiple theories
• Lithium strengthens the calm neurons and calms the excited neurons".
• Most efficacious in classic BPD
• Takes 5-10 days to take effect.
• Antipsychotic and/or benzodiazepine is used for the initial treatment of mania until lithium takes affect.
• Prevents relapse (not 100%).
• Reduces the risk of suicide.
• Reduces aggression/impulsivity.
• Reduces the risk of developing neurocognitive disorder.
• Increase in gray matter and hippocampus in patients taking lithium.

Lithium Side Effects

• The trough blood level should be adjusted and maintained between 0.6-1.2 mmol/L (“lithium one.2").
• Check serum trough level right before the next dose.
• Narrow therapeutic index; toxic levels can be fatal and can be close to therapeutic levels.
• Lithium is contraindicated in several patient populations
  • Significant renal impairment
  • Sodium depletion
  • Dehydration
  • Significant cardiovascular disease
  • Hypothyroidism
  • Pregnancy
• Read the package insert before administration.
• Side effects covered by LMNOP.
• L: Lithium
• M: Movement (tremor/ neuro symptoms)
• N: Nephrotoxicity (and diabetes insipidus)
• O: hypothyroidism
• P: Pregnancy: teratogenic, increased risk of Ebstein's anomaly (LIThium: low implanted tricuspid)
• The side effects are typically "Twitchy (GI and neuro) with pissy renal and diabetes insipidus"

Lithium Side Effects

• The following side effects can occur from lithium:
  • Nausea, diarrhea
  • Polyuria and thirst
  • Weight gain
  • Edema
  • Worsening psoriasis
  • Cognitive impairment.. and others
  • With over-dose, worsening neuro symptoms: ataxia, seizures, coma, death
• Medical illness, especially diarrhea, vomiting, or anorexia
• Surgery metabolic aberrations
• Severely restrictive dieting, sodium restriction diet with inverse proportion
• With increased sodium intake
• Strenuous exercise increased perspiration, dehydration, hot climate
• Advanced age
• Inverse relationship to sodium level: higher the sodium, lower the lithium level and visa versa.

Required Labs after lithium adminsitration

• CBC with differential
• Comprehensive metabolic panel
• UA
• BUN/ Creatinine
• TSH/ Thyroid function studies
• Calcium
• Pregnancy test for women of childbearing potential
• ECG for patients > 40 or ↑CV risks

Managing Lithium Side Effects

• Watchful waiting - tolerance to some side effects (nausea and tremor) can occur, but unlikely with weight gain.
• Changing the time of administration.
• Lowering the dose (dose reductions risk compromising efficacy).
• Changing to a different form of lithium (immediate or slow release).
• Dividing the daily dose to take smaller amounts more often decreases peak serum levels.
• Discontinuing and switching to an anticonvulsant if side effects are intolerable.

Lithium Drug Interactions

• Drug interactions are an important review if the patient is on lithium.
• Increases lithium level:
  • Thiazide diuretics
  • Nonsteroidal anti-inflammatory drugs, except aspirin
  • Angiotensin-converting enzyme inhibitors
  • Antibiotics tetracyclines and metronidazole
• Decreases lithium level:
  • Potassium-sparing diuretics
• May increase or decrease lithium level:
  • Loop diuretics

BPD Treatment - Anticonvulsants

• Decreases firing of CNS nerves by inhibiting voltage gated sodium channels.
• Increases GABA allowing for the calming, MOA of hypnotics/tranquilizers.
• Alternative to, or used if there is a previous poor response to, lithium.
• Used when the patient has recurrent substance abuse.
• All anticonvulsants are teratogenic.

BPD Treatment - Valproic Acid, Divalproex (Depakote)

• Some sources consider DOC (drug of choice).
• Used for rapid cyclers.
• Blood levels are monitored for a therapeutic range.
• Side effects include weight gain, nausea, vomiting, hair loss, easy bruising, tremor, drowsiness, fatigue, skin rash, and gait disturbance.
• Divalproex is enteric coated, contains valproic acid and valproate; it is better on the GI track and more expensive.
• PATHological Side Effects include:
  • Pancreatitis
  • Aplastic anemia risk/ low platelet count
  • Teratogenic: neural tube defect and others Valpro ATE the folate
  • Hepatic toxicity potential: hepatic failure risk
• The schedule doesn't need to be memorized for the exam, just remember the required labs.

Carbamazepine

• Indicates for mixed features or as an alternative medication.
• Side effects include diplopia and ataxia (most common), GI symptoms (nausea, vomiting, diarrhea), weight gain, hyponatremia, rash, and pruritus, and elevated liver enzymes.
• Photosensitivity is induced.
• Memory cue: This will "Take Control of mixed features"
• Can lead to blood dyscrasias
• In rare instances can case Aplastic anemia andleukopenia.
• Life-threatening Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), especially in the first 8 weeks of therapy.
• Screen Asian patients for HLA-B*1502 prior to adminsitration.

BPD Treatment – Lamotrigine (Lamictal)

• Used for predominately depressive BP 1 or 2 or rapid cycling.
• Can cause weight loss.
• Can lead to SJS/TEN.
• Primarily used to treat the “lows”.

Psychosis

• Only 5 FDA-approved for bipolar: cariprazine (Vraylar®), lurasidone (Latuda®), olanzapine-fluoxetine combination (Symbyax®), quetiapine (Seroquel®), and lumateperone Caplyta®)
• Combo: fluoxetine and olanzapine combo (Symbyax)
• Olanzapine: antipsychotic, significant weight gain.
• Quetiapine (Seroquel)
• Antipsychotic
• Recent FDA approved single treatment for mania and depression

BPD Agitation and/or Insomnia

• Benzodiazepines are used for treatment
• Clonazepam or lorazepam can be used specifically
• Sleep hygiene
• Low dose trazadone
• Insomnia is a risk factor for BPD
• For recalcitrant/ difficult-to-control cases

Electroconvulsive Therapy (ECT)

• ECT has been seen to be a very effective treatment option.

Bipolar Disorder During Pregnancy

• First generation antipsychotic medications can be used during pregnancy, like haloperidol (haldol)
  • It is a relatively safe option but has increased risk for Extrapyramidal and uncomfortable side effects
• Second generation antipsychotic medication is generally preferred.
  • As long as the patient is enrolled in a National Registry for Atypical Antipsychotics.
  • Can be used as they are typically safer than lithium/anticonvulsants.
• Lithium presents an increased risk for teratogenic defects especially in the first trimester.
  • Only use with close follow up and ultrasound.
• If a patient is on anticonvulsants remind a patient to have increased folate intake
• ECT is safe and effective
• Any patient that is pregnant or considering should be treated by a perinatologist and psychiatrist.

General Guidelines

• Bipolar I consists of
  • Manic episodes
  • Almost always is associated with depression, can have euthymia mood between the two.
  • Lithium or Anticonvulsant are used as mood stabilizers, with SGA and lamotrigine if the patient has predominately depressive symptoms.
• Bipolar II can show depression more then 2 months,
  • With periods of hypomania as shown, depression can be seen as debilitating in most patients 3 symptoms for at least 4 days to be considered, no psychotic symptoms can show..hypomania, so social occupational ability is mostly ok.
  • Is a low dose option,
• Cycling must be done with care as there can be an increased risk for BPD 1 and 2

Bipolar Treatment for Patients with Primarily Depression

• Anti-depressants alone, typically, are mostly ineffective
• Increases the change for "manic attacks"

Lithium Management Tips

• Breakthrough can occur and you must keep monitoring for changes

BPD Treatment - Adherence

• Approximately 50% of patients stop taking medication, with the average time to non-adherence being about 9 months
• This is due to a few main points
  • High Costs
  • Increased side effects
  • Hating the change in medications
• Some bipolar artists feel their creative work is stifled while on lithium, or mention emotional changes, due to this patient's do not continue with there treatment and it can become a re occurring event for which hospitalization can occur and for some patient is better lifestyle change but with help to monitor there actions.

BPD Lifestyle Changes

• A few modifications that patients can do on a daily bases can give big turn around as they work with doctors in medication stability and management
  • Anti inflammatory lifestyle (diet)
  • no rugs no alcohol and cut the caffeine
  • Work on increasing your exercise
  • Rest sleep schedule
  • Work on talking to supports channels and groups
  • Contact support channels, groups, and family
  • Work with counselors a better means to achieve the best outcome
  • Look for ways to learn about trigger points
• Can find the cci modules online to help for self discovery and preventing a possible setback.

Test your knowledge of Bipolar Disorder with this quiz. Questions cover symptoms, onset age, biological factors and risk factors like genetic predisposition and substance use. Understand the implications of these factors for early intervention and mortality rates.