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1. DRUGS USED IN THE TREATMENT OF
AFFECTIVE DISORDERS
Dr Sitanimezi Mweenda-Chikuta
Lecturer, Pharmacology

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Affective disorders are a group of psychoses associated with
changes of mood:
Unipolar depression
Bipolar disorder (manic-depressive illness)
Various groups of drugs are used in the drug treatment of affective
disorders
Anti-depressants are used in treatment of unipolar depression and in
the depressive phase of bipolar disorder
Anti-psychotic drugs, carbamazepine and lithium are used in the
manic phase of bipolar disorder
Some anti-seizure drugs (carbamazepine, valproate and gabapentin)
and lithium are used to stabilize the mood in bipolar disorder
INTRODUCTION

3. LEARNING OBJECTIVES
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Classify anti-depressant drugs
Describe the molecular mechanisms that account for the
anti-depressant actions of anti-depressant drugs
Describe the mechanisms of action, adverse effects,
precautions and contraindications of the various classes
of anti-depressant drugs
Outline the drug treatment of bipolar disorder
Describe the relevant clinical pharmacology of lithium

4. ANTI-DEPRESSANTS
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Drugs used in the treatment of unipolar depressive
episodes and depressive phase in bipolar disorder are
classified into four groups:
Tricyclic anti-depressants (TCAs)
Selective serotonin reuptake inhibitors (SSRIs)
Monoamine oxidase inhibitors (MAOIs)
Atypical anti-depressants
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5. MECHANISMS OF ANTI-DEPRESSANT ACTION
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Anti-depressant therapeutic efficacy is closely associated
with:
Decreased cyclic AMP
Reduction (down-regulation) of post-synaptic beta-
adrenoceptors
Increased responsiveness of post-synaptic serotonin 5-
HT1A receptors
Desensitization of presynaptic noradrenaline and
serotonin auto-receptors
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6. ANTI-DEPRESSANT DRUGS …. CONT’D
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All anti-depressants have similar therapeutic efficacy,
although individual patients may respond better to one
drug than another
All anti-depressants have delayed therapeutic efficacy
– effects are seen after 2-4 weeks
Selection is based on patient co-morbidities,
associated adverse effects, drug interactions, drug-
food interactions, contra-indications and patient
preference
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7. TRICYCLIC ANTI-DEPRESSANTS AND RELATED DRUGS
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Include amitriptyline, imipramine, nortriptyline, desipramine,
dosulepin (dothiepine) and lofepramine
Mechanism of action: 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)
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8. TRICYCLIC ANTI-DEPRESSANTS …. CONT’D
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Adverse effects: Dry mouth, blurred vision, constipation,
postural hypotension, increased risk of arrhythmias,
sedation, weight gain
Overdose: Arrhythmias, shock, respiratory depression,
seizures, coma and death (have a narrow therapeutic index)
Contraindications: Arrhythmias, recent myocardial infarction,
manic phase, severe liver disease, seizure disorders, and
patients taking lignocaine, anticholinergic drugs or alcohol
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9. SELECTIVE SEROTONIN REUPTAKE INHIBITORS
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Include flouxetine, fluvoxamine, citalopram, paroxetine and
sertraline
Mechanism of action: 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
Preferred in elderly patients because of low anti-muscarinic
effects
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10. SELECTIVE SEROTONIN REUPTAKE INHIBITORS:
ADVERSE EFFECTS
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Headache, nausea, vomiting, diarrhoea, insomnia, anxiety,
agitation, sexual dysfunction
May induce suicidal ideation in children, adolescents and
young adults
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11. MONO-AMINE OXIDASE INHIBITORS
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Include phenelzine, tranylcypromine, isocarboxazide and
moclobemide
Mechanism of action
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
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12. MONO-AMINE OXIDASE INHIBITORS
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Indications: Used for depression refractory to other
antidepressants
Adverse effects: Headache, CNS excitement, tremors,
postural hypotension, dry mouth, blurred vision, sexual
dysfunction (phenelzine), weight gain and sleep
disturbances
Overdose: Agitation, hyperthermia, seizures, hypotension or
hypertension
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13. MAO INHIBITORS: DRUG AND FOOD INTERACTIONS
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Inhibition of metabolism of sympathomimetic amines
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.
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14. MAO INHIBITORS: OTHER DRUG INTERACTIONS
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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
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15. MISCELLANEOUS ANTI-DEPRESSANT DRUGS
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Venlafaxine: 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.
Reboxetine: Selectively inhibits reuptake of noradrenaline
Mirtazapine: Blocks alpha2-adrenoceptors thereby increasing
noradrenaline release. Is very sedative and causes weight
gain.
Trazodone: Inhibits serotonin reuptake. Adverse effects
include postural hypotension and priapism. Safer than TCAs
in overdose.
Nefazodone: Inhibits serotonin reuptake. Causes sedation
and mild postural hypotension. Used in the prophylaxis of
recurrent depression.
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16. TREATMENT OF BIPOLAR DISORDER
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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
Mood stabilizers include lithium, carbamazepine, valproate,
lamotrigine and gabapentin
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17. TREATMENT OF BIPOLAR DISORDER
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Carbamazepine
Effective in prophylaxis of bipolar disorder and treatment of
acute mania
Can be combined with lithium for enhanced therapeutic
effects
Valproate
Can be used as monotherapy in mild to moderate cases and in
combination with lithium in refractory cases
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18. LITHIUM
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Mechanism of action
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
It is a mood stabilizer and suppresses acute mania
Clinical indications
(1) Prophylaxis and treatment of bipolar disorder (2)
Prophylaxis and treatment of acute mania (3) Prophylaxis of
resistant recurrent depression
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19. LITHIUM: ADVERSE EFFECTS
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Lithium has a narrow therapeutic window and adverse
effects are common. Plasma concentration monitoring is
essential to avoid toxicity.
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
Over-dosage: Delirium, muscle twitching, convulsions,
arrhythmias and renal failure and death
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20. LITHIUM …. CONT’D
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Treatment of lithium toxicity: Discontinue lithium
administration, haemodialysis and anti-convulsants
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
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21. END
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