Antidepressants

Question 1

Types of antidepressants

Answer 1

• MAOIs
• TCAs
  (imipramine, amitriptyline, nortriptyline)
• SSRIs,
  (fluoxetine, citalopram)
• selective NA uptake inhibitors, (NARI)
  (reboxetine)
• non-selective 5HT/NA uptake inhibitors (SNRI)
  (venlafaxine, duloxetine)

Mirtazapine
Bupropion
Agomelatine
Ketamine

Question 2

Major clinical depression causes

Answer 2

Major cause of work days lost to disability.

Major cause of premature death.

Question 3

Symptoms of depression

Answer 3

 Emotional
• Misery, apathy, and pessimism
• Low self-esteem (feelings of guilt, inadequacy and ugliness)
• Indecisiveness, loss of motivation

 Other domains
• Retardation of thought and action
• Loss of libido
• Sleep disturbance and loss of appetite

duration of symptoms >6months

Question 4

Types of depression

Answer 4

 Unipolar depression
• Mood swings always in the same direction

 Bipolar depression or affective disorder
• Alternating depression and mania

Question 5

Types of Unipolar depression

Answer 5

 Reactive Depression (about 75 % of cases)

• non-familial
• associated with life-events
• accompanied by symptoms of anxiety and agitation
anxiety and depression hard to differentiate normally co-exist

 Endogenous Depression (about 25 % of cases)
• familial pattern
• not directly related to external stress

Question 6

Reactive depression

Answer 6

 Reactive Depression (about 75 % of cases)

• non-familial
• associated with life-events
• accompanied by symptoms of anxiety and agitation
anxiety and depression hard to differentiate normally co-exist

UNIpolar

Question 7

endogenous depression

Answer 7

 Endogenous Depression (about 25 % of cases)
• familial pattern
• not directly related to external stress

UNIpolar

Question 8

bipolar depression

Answer 8

 Depression alternates with mania
 Periodicity of oscillations in mood vary but usually occur over several weeks
 Usually appears in early adulthood
 Strongly familial
 Some studies suggest genetic similarities to susceptibility to schizophrenia
 Drugs used to treat depressive symptoms still usually include antidepressants

Question 9

theory to explain depression

Answer 9

Monoamine theory
 Deficits in monoamine neurotransmitters (noradrenaline and 5-HT) cause depression.
 Basis of most successful pharmacological strategies for treatment of depression.

• observed from reserpine which inhibits NA and 5-HT storage, depressed mood.

Question 10

limitation of monoamine theory

Answer 10

 Hypothesis originally formulated for noradrenaline, but later emphasis shifted to 5-HT.

 Studies of monoamine markers in depressed patients have yielded inconsistent and equivocal results.

 Monoamine hypothesis alone is inadequate to explain all pharmacological actions in depression

Question 11

Monoamine oxidase (MAO)

Answer 11

 Found in nearly all tissues, including nerve terminals, intestine, and liver.
 Found intracellularly, mostly on the mitochondrial surface.
 Breaks down monoamines.

Two major forms, MAO-A and MAO-B:
 5-HT broken down mainly by MAO-A.
 Both forms act on noradrenaline (NA) and dopamine.

MAO-B selective inhibitors (e.g. selegiline) are used in Parkinson’s disease.

 MAO inhibitors (MAOIs) increase biological availability of monoamines.
 MAOIs such as phenelzine are used as antidepressants.

Phenelzine is:
 Non-selective for MAO-A versus MAO-B.
 An irreversible MAO inhibitor.

Question 12

Tricyclic Antidepressants (TCAs)

Answer 12

Initially produced as potential antipsychotic drugs in 1949 but found to be ineffective in schizophrenia.

Non-selective for SERT/NET:
Imipramine, Amitriptyline, nortriptyline

Selective for NET:
Desipramine

SERT: serotonin transporter
NET: norepinephrine transporter

Question 13

Nortriptyline

Answer 13

 Second generation TCA
 Milder side effects compared to amitriptyline and imipramine
 Improved compliance

Question 14

Selective Serotonin reuptake Inhibitors (SSRIs) are the first drug class developed for the purpose of antidepressant treatment

Answer 14

Selective Serotonin reuptake Inhibitors (SSRIs) are the first drug class developed for the purpose of antidepressant treatment

Question 15

SSRI

Answer 15

 Greater 5-HT reuptake selectivity than TCAs.
 50- to 1000-fold selectivity for 5-HT over NA.
 Fluoxetine approximately 50-fold selectivity for 5-HT.  Citalopram approximately 1000-fold selectivity for 5-HT.

 Fewer adverse effects than TCAs.

Question 16

currently the most widely prescribed antidepressant.

Answer 16

Fluoxetine

Question 17

Noradrenaline Reuptake Inhibitors (NARIs)

Answer 17

 Greater NA reuptake selectivity than TCAs.
 Approximately 1000-fold selectivity for NA over 5-HT.  Reboxetine approximately 1000-fold selectivity for NA.
 Fewer adverse effects than TCAs and SSRIs.

Question 18

Serotonin and Noradrenaline reuptake Inhibitors (SNRIs)

Answer 18

 Similar dual 5-HT and NA reuptake inhibition profiles to non-selective TCAs.
 Issue of additional receptor antagonism is controversial.
 Venlafaxine, desvenlafaxine(synthetic metabolite of venlafaxine) and duloxetine are examples in clinical use.