Drugs Used In The Treatment Of Affective Disorders

Question 1

What is bipolar disorder?

Answer 1

Bipolar disorder is a mental illness marked by extreme shifts in mood ranging from a manic to a depressive state.
A person with mania will feel excited, impulsive, euphoric, and full of energy. He or she might engage in risky or unhealthy behavior. Drug use, spending sprees, and impulsive or unprotected sex are common during manic episodes
The depressive episodes might bring on deep sadness and hopelessness. Depression causes a loss of energy and interest in activities the patient once enjoyed.
This phase can include periods of too little or too much sleep. Also, suicidal thoughts or attempts may come with deep depression

Question 2

Briefly describe the types of bipolar disorders

Answer 2

1. Bipolar I disorder will show at least one manic episode and one or more major depression episodes. Bipolar I disorder is equally common in men and women. The first episode in men is usually mania. In women, the first episode is typically major depression
2. bipolar II experience major depression. But instead of mania they experience hypomania. With hypomania, a person will still exhibit high energy, impulsiveness, and excitability. However, the mood is not as extreme as full-fledged mania, and these patients never experience hallucinations or delusions during a hypomanic episode.
3. Cyclothymic Disorder This is a “mild” form of bipolar disorder, with mood swings that are less severe and episodes shifting from hypomania to mild depression

Question 3

What are the common signs and symptoms of mania?

Answer 3

Feeling unusually “high” and optimistic or extremely irritable
Unrealistic, grandiose beliefs about one’s abilities or powers
Sleeping very little, but feeling extremely energetic
Talking so rapidly that others can’t keep up
Racing thoughts; jumping quickly from one idea to the next
Highly distractible, unable to concentrate
Impaired judgment and impulsiveness
Acting recklessly without thinking about the consequences
Delusions and hallucinations (in severe cases)

Question 4

What common symptoms of bipolar depression?

Answer 4

Feeling hopeless, sad, or empty
Irritability
Inability to experience pleasure
Fatigue or loss of energy
Physical and mental sluggishness
Appetite or weight changes
Sleep problems
Concentration and memory problems
Feelings of worthlessness or guilt
Thoughts of death or suicide

Question 5

Depression is secondary to…?

Answer 5

1. Organic problems like hypothyroidism, dementia, anemia
2. Psychiatric problems like schizophrenia, drug abuse, anxiety disorders
3. Use of depressants drugs such as alcohol

Question 6

Describe the monoamine hypothesis of depression

Answer 6

The first major theory about the biological aetiology of depression hypothesized that depression was due to a deficiency of monoamine neurotransmitters, notably norepinephrine (NE), dopamine (DA) and Serotonin

Question 7

Which classes of drugs are used to treat affective disorders?

Answer 7

Anti-psychotic drugs
Anti-seizure drugs
Antidepressants

Question 8

Which antidepressants are used to treat affective disorders?

Answer 8

1. Tricyclic anti-depressants (TCAs)
2. Selective serotonin reuptake inhibitors (SSRIs)
3. Monoamine oxidase inhibitors (MAOIs)
4. Atypical anti-depressants

Question 9

List the TCAs used

Answer 9

amitriptyline,
imipramine,
nortriptyline,
desipramine,
dosulepin (dothiepine) and
lofepramine

Question 10

What is the MoA of TCAs?

Answer 10

Block uptake of noradrenaline and 5-HT into the presynaptic terminal (inhibit the re-uptake pumps)
TCAs also block muscarinic, histamine H1 and alpha-adrenergic receptors (this contributes to their unwanted effects)

Question 11

What are the adverse effects of TCAs?

Answer 11

Dry mouth, blurred vision, constipation, postural hypotension, increased risk of arrhythmias, sedation, weight gain

Question 12

What are the results a TCA overdose?

Answer 12

Arrhythmias, shock, respiratory depression, seizures, coma and death (have a narrow therapeutic index)

Question 13

What are the contraindications of TCAs?

Answer 13

Arrhythmias, recent myocardial infarction, manic phase, severe liver disease, seizure disorders, and patients taking lignocaine, anticholinergic drugs or alcohol

Question 14

List the SSRIs used

Answer 14

flouxetine, fluvoxamine, citalopram, paroxetine and sertraline

Question 15

What is the MoA of SSRIs?

Answer 15

Selectively inhibit the reuptake of serotonin into presynaptic nerve terminals
Similar efficacy to TCAs
They are better tolerated than TCAs and MAO inhibitors, and are safer in overdose

Question 16

What are the adverse effects of SSRIs?

Answer 16

Headache, nausea, vomiting, diarrhoea, insomnia, anxiety, agitation, sexual dysfunction
May induce suicidal ideation in children, adolescents and young adults

Question 16

List the MAOIs used

Answer 16

phenelzine, tranylcypromine, isocarboxazide and moclobemide

Question 17

What is the MoA of MAOIs?

Answer 17

Inhibit monoamine oxidase (MAO), the enzyme that metabolizes monoamines (noradrenaline, serotonin and dopamine)
Inhibition of MAO-A which preferentially degrades norepinephrine and serotonin is responsible for the therapeutic efficacy of MAOIs (MAO-B degrades dopamine preferentially)
Moclobemide is selective for MAO-A

Question 18

What are the adverse effects of MAOIs?

Answer 18

Headache, CNS excitement, tremors, postural hypotension, dry mouth, blurred vision, sexual dysfunction (phenelzine), weight gain and sleep disturbances

Question 19

What is the result of an MAOI overdose?

Answer 19

Agitation, hyperthermia, seizures, hypotension or hypertension

Question 20

Describe the drug food interaction of MAOIs

Answer 20

MAOIs inhibit the metabolism of indirectly acting sympathomimetic drugs (e.g. phenylephrine, ephedrine and pseudoephedrine) and tyramine from certain foods such as cheese, mature wines, yeast, fish, sausages). These amines are metabolized by MAO.
The result of the inhibition is severe hypertension and arrhythmias. These effects are due to increased noradrenaline release resulting from increased levels of the amines.

Question 21

Describe the drug-drug interaction of MAOIs

Answer 21

MAOIs interact with SSRIs, TCAs, tramadol and pethidine resulting in the “serotonin syndrome” (characterised by tremor, hyperthermia, muscle rigidity and cardiovascular collapse)
MAOIs result in additive sedation and CNS depression when given concurrently with benzodiazepines, barbiturates, ethanol and opioids

Question 22

Briefly write on the use of Venlafaxine

Answer 22

Inhibits reuptake of noradrenaline and serotonin. Adverse effects include nausea, dizziness, sexual disturbances, anxiety and insomnia. Useful in patients not responding to other anti-depressants.

Question 23

Briefly write on the use of Reboxetine

Answer 23

Selectively inhibits reuptake of noradrenaline

Question 24

Briefly write on the use of Mirtazapine

Answer 24

Blocks alpha2-adrenoceptors thereby increasing noradrenaline release. Is very sedative and causes weight gain

Question 25

Briefly write on the use of Trazodone

Answer 25

Inhibits serotonin reuptake. Adverse effects include postural hypotension and priapism. Safer than TCAs in overdose

Question 26

Briefly write on the use of Nefazodone

Answer 26

Inhibits serotonin reuptake. Causes sedation and mild postural hypotension. Used in the prophylaxis of recurrent depression

Question 27

What is the treatment plan for bipolar?

Answer 27

Bipolar disorder is treated with a combination of mood stabilizers and anti-depressants, and sometimes anti-psychotics (anti-psychotics are given during the manic phase)
Mood stabilizers prevent mood swings that are seen in bipolar disorder

Question 28

Which mood stabilizers are used in the treatment of bipolar?

Answer 28

lithium, carbamazepine, valproate, lamotrigine and gabapentin

Question 29

What is the MoA of lithium?

Answer 29

Inhibits inositol monophosphate, thereby decreasing the activity of the second messengers diacylglycerol and inositol-1,4,5-triphosphate
Has anti-manic and anti-depressant activity

Question 30

What are the clinical indications of lithium?

Answer 30

(1) Prophylaxis and treatment of bipolar disorder
(2) Prophylaxis and treatment of acute mania
(3) Prophylaxis of resistant recurrent depression

Question 31

What are the adverse effects of lithium?

Answer 31

Adverse effects include thirst, nausea, vomiting, diarrhoea, tremor and polyuria. Late adverse effects include weight gain, oedema, acne, nephrogenic diabetes insipidus and hypothyroidism.
High plasma concentrations result in drowsiness, confusion, ataxia, blurred vision, nystagmus and seizures

Question 32

What are the results of a litium overdose?

Answer 32

Delirium, muscle twitching, convulsions, arrhythmias and renal failure and death

Question 33

How do you treat lithium toxicity?

Answer 33

Discontinue lithium administration, haemodialysis and anti-convulsants

Question 34

What are the contraindications of lithium?

Answer 34

Contraindications: Antipsychotics, NSAIDs, diuretics, pregnancy, breastfeeding
Diuretics deplete sodium and this depletion results in increased renal reabsorption of lithium thereby increasing lithium toxicity
NSAIDs decrease the renal clearance of lithium resulting in increased risk of toxicity