Module 3 Section 4 (Bipolar Disorder)

Question 1

What is bipolar disorder?

Answer 1

Bipolar disorder (once known as manic depressive disorder) is a brain disorder characterized by manic and depressive phases.

Question 2

True or false: bipolar disorder occurs in about 1% to 3% of the population.

Answer 2

True

Question 3

What are the symptoms of bipolar disorder?

Answer 3

Symptoms associated with the manic phase are elation, excitement, hyperactivity, disinhibition, aggression, and some psychotic symptoms.

In the depressive phase, the symptoms are similar to major depressive disorder, with the key features being depressed mood, sleep disturbances, and anxiety.

Patients with bipolar disorder are at a high suicide risk.

Question 4

What is the 2-step process for treating the manic phase of bipolar disorder?

Answer 4

1) Reduce the patient’s mood to a “normal” range with antipsychotic medications such as haloperidol, chlorpromazine, or new atypical antipsychotics.
2) Stabilize the patient’s mood within “normal” range with a mood stabilizer.

Question 5

How does treatment for the different phases of bipolar disorder differ?

Answer 5

The depressive phase of bipolar disorder is not the same as major depression.

As such, antidepressants are sometimes used, but may actually make matters worse. Mood stabilizers tend to be effective in the depressive phase.

Question 6

What types of drugs are used for bipolar disorder?

Answer 6

Two type of drugs are typically used in the treatment of bipolar disorder, antipsychotics and mood stabilizers.

Question 7

What are antipsychotics?

Answer 7

Antipsychotics are a class of drugs used to reduce psychotic symptoms caused by a variety of disorders, including bipolar disorder, schizophrenia, and drug-induced psychoses.

Question 8

What are the 3 classes of antipsychotics?

Answer 8

1) Phenothiazine antipsychotics
2) Haloperidol
3) Atypical antipsychotics

Question 9

How do phenothiazine antipsychotics work?

Answer 9

Phenothiazine antipsychotics exert their therapeutic effect by blocking dopamine receptors.

Antagonism of dopamine receptors in the mesolimbic and mesofrontalregions of the brain helps to alleviate some of the symptoms associated with psychosis, such as unusual or bizarre behaviour, thought disorder, and delusions.

Question 10

What are some adverse effects of phenothiazine antipsychotics?

Answer 10

Antagonism of dopamine receptors in the nigrostriatal system of the brain results in extrapyramidal movement disorders. These include:

• tremor
• rigidity of limbs and slowing of movement
• reduction in spontaneous activity
• dystonia (involuntary muscle spasms)
• akathesia (anxiety, restlessness, and repetitive purposeless action)
• Tardive dyskinesia (a serious movement disorder that can occur and is characterized by involuntary movements of the face, tongue, trunk, and limbs, and can be severely disabling).

Antagonism of dopamine receptors in the hypothalamus will result in excess release of prolactin.

• In women, this will result in the flow of milk from the breast and menstrual changes
• In men it will cause sexual dysfunction.

Question 11

Explain the cause of the therapeutic and adverse effects of phenothiazine antipsychotics.

Answer 11

The therapeutic and adverse effects of the phenothiazines are primarily due to antagonism of dopamine receptors in different regions of the CNS.

However, this class of drugs is not highly specific to dopamine receptors, therefore some effects (both therapeutic and adverse) are related to activation of other receptor systems, such as cholinergic, histaminic, and alpha-adrenergic receptors.

Question 12

Phenothiazine antipsychotics can also antagonize other receptors in the brain. What are they?

Answer 12

Blockade of Cholinergic (muscarinic) receptors:

• Therapeutic effects: reduction of extrapyramidal adverse effects.
• Adverse effects: blurred vision, dry mouth, constipation, difficulty urinating.

Blockade of Histamine Receptors:
- Adverse effects: sedation, drowsiness, and weight gain.

Blockade of α-adrenoceptors:
- Adverse effects: postural hypotension, dizziness, reflex tachycardia.

Question 13

How does haloperidol work?

Answer 13

Like the phenothiazines, haloperidol competitively blocks dopamine receptors.

Therefore, haloperidol has very similar pharmacological effects to the phenothiazines.

Question 14

True or false: the sedative and hypotensive actions observed with haloperidol are less than that observed with phenothiazines.

Answer 14

True

But it has a high propensity for producing extrapyramidal movement disorders. It is considered a useful alternative for patients who do not respond to or cannot tolerate phenothiazines.

Question 15

How do atypical antipsychotics work?

Answer 15

It is thought that these second-generation antipsychotics have a dual action by blocking dopamine and serotonin receptors.

Question 16

What are some examples of atypical antipsychotics (2nd generation)?

Answer 16

clozapine, risperidone, and olanzapine.

Question 17

What are some adverse effects of atypical antipsychotics?

Answer 17

Atypical antipsychotics, or second-generation antipsychotic agents, produce less extrapyramidal side effects.

Prominent side effects of the second-generation antipsychotics are:

• weight gain
• increased risk of developing diabetes
• sudden cardiac death due to an abnormality in the rhythm of the heart

Question 18

What are some other uses of atypical antipsychotics?

Answer 18

The atypical antipsychotics have been used in other conditions, such as treating:

• schizophrenia
• delusions and aggression associated with dementia in the elderly
• autism spectrum disorder
• developmental disorder
• posttraumatic stress disorder (as an alternate to antidepressants)
• obsessive compulsive disorder
• borderline personality disorder

Question 19

Using the information provided, select which antipsychotic agent would be the most appropriate choice to begin therapy in a patient with bipolar disorder.

Patient information:

• Age: 48
• Gender: Female
• Current Status: Patient has severe symptoms of bipolar disorder
• Additional Information: Patient has a diagnosed cardiac arrhythmia

Answer Options:

a) Haloperidol
b) Thorazine (Phenothiazine)
c) Olanzapine (atypical antipsychotic)

Answer 19

b) Thorazine (Phenothiazine)

The potential of sudden cardiac death due to an abnormal heart rhythm that is associated with some atypical antipsychotics may be dangerous for this individual given their current heart condition. Haloperidol is often prescribed when phenothiazines fail. Therefore, a phenothiazine drug such as thorazine may be a good choice of antipsychotic to begin with.

Question 20

What are mood stabilizers?

Answer 20

Mood stabilizers are the second category of drugs used to treat bipolar disorder. They are commonly used to prevent the mania (highs) and depression (lows) associated with bipolar disorder.

Question 21

What are the 2 categories commonly used for mood stabilizers?

Answer 21

Lithium carbonate, and anticonvulsants

Question 22

What is lithium carbonate?

Answer 22

Lithium carbonate is a mood-stabilizing agent used to prevent mood swings in patients with bipolar disorder. It is also used to treat mania.

Question 23

What are the 2 possible explanations for the mechanism of action for lithium carbonate?

Answer 23

1) Effect on electrolytes and ion transport.
2) Effect on second messengers that mediate transmitter action.

The evidence appears to be the strongest for the second possibility.

Question 24

Discuss the pharmacokinetics of lithium.

Answer 24

A period of 2-4 weeks of lithium administration may be required for lithium to have a full therapeutic effect.
- Acutely, manic patients often require temporary treatment with an antipsychotic drug, such as haloperidol, or an anti-anxiety drug, such as a benzodiazepine.

The body eliminates lithium as if it were sodium. As such, increased sodium intake increases lithium excretion.
- In addition, lithium has a narrow therapeutic index. Therefore the safety and efficacy of lithium is enhanced by monitoring serum lithium concentration. Measurements should be made approximately 12 hours after the last dose.

Question 25

What are the adverse effects of lithium?

Answer 25

• Tremor, thirst, excessive urination, edema, and weight gain may persist for the duration of treatment.
• Confusion and loss of muscle coordination.
• Mild hypothyroidism.
• Toxic kidney effects are observed in some individuals treated chronically with lithium, but are uncommon.
• When taken during pregnancy, it can, as a rare event, cause cardiac malformations in the fetus.

Question 26

What is the clinical use of lithium?

Answer 26

Lithium was once the drug of choice for long-term maintenance to prevent both manic and depressive episodes in patients with bipolar disorder, however, the side effects and toxicities are relegating it to second-line therapy.

Interestingly though, of all medications with demonstrated efficacy for treatment of bipolar disorder, lithium has the greatest efficacy for prophylaxis of future manic and depressive episodes.

Furthermore, lithium is the only medication that has demonstrated a reduction in suicidality among bipolar patients.

Question 27

How are anticonvulsants used as mood stabilizers?

Answer 27

The anticonvulsants, such as valproic acid, have been found to be useful agents as mood stabilizers. These agents have a more rapid onset of action than lithium, and are often preferred. It is important to note that not all anticonvulsants are mood stabilizers.

The depressive phase of bipolar disorder can sometimes be treated with antidepressants.

Question 28

Some antidepressants can cause mania. What are some examples?

Answer 28

TCAs have been linked to inducing mania.

SSRIs are less likely to induce mania, but research indicates that they may have limited efficacy for the depressive phase of bipolar disorder.

As such, the depressive phase of bipolar disorder is often effectively treated with mood stabilizers instead of antidepressants.

Question 29

Which one of the statements regarding bipolar disorder is correct?

a) The depressive phase of bipolar disorder is the exact same as major depression.
b) Mood stabilizers are rarely used in the treatment of bipolar disorder.
c) Bipolar disorder is usually associated with manic and depressive phases.
d) Lithium carbonate has very few adverse effects.

Answer 29

c) Bipolar disorder is usually associated with manic and depressive phases.