Contents of antidepressants

1. Introduction to Antidepressant drugs

2. Classes of antidepressant drugs

• Tricyclic and related antidepressant drugs
• MonoamineOxidase Inhibitirs (MAOIs)
• Selective Serotinin Reuptake Inhibitors (SSRIs)
• Other antidepressant drugs.

3. Mechanisms of actions of antidepressants

4. Common side effects of antidepressants

5. Tricyclic and related antidepressant drugs

• Amitriptyline Hydrochloride
• Amoxapine
• Clomipramine Hydrochloride
• Dosulepin Hydrochloride
• Doxepin
• Imipramine Hydrochloride
• Lofepramine
• Nortriprtyline
• Trimipramine

6. Monoamine Oxidase Inhibitors

• Phenelzine
• Isocarboxazid
• Tranylcypromine
• Moclobemide

7. Selective Serotonin Reuptake Inhibitors

• Citalopram
• Escitalopram
• Fluoxetin
• Fluvoxamine maleate
• Paroxetine
• Sertraline

8. Other antidepressant drugs

• Flupentixol
• Mirtazapine
• Reboxetine
• Tryptophan
• Venlaflaxine

9. Drug interactions

• Drugs interactions with Tricyclic and related antidepressant drugs
• Drugs interactions with MonoamineOxidase Inhibitirs (MAOIs)
• Drugs interactions with Selective Serotinin Reuptake Inhibitors (SSRIs)
• Drugs interactions with other antidepressant drugs.

10. New developments

Introduction to Antidepressant drugs

Antidepressant drugs are effective in the treatment of major depression ofmoderate and severe degree including major depression associated with physical illness and that following child birth; they are also effective for dysthymia (low grade chronic depression).antidepressant drugs are not generally effective in milder forms of acute depression but trial may be considered in cases of refractory to psychological treatment.

Choice of antidepressant should be based on the individualpatient’srequirements, including the presence of concomitant diseases, exixting therapy, suicide risk, and previous response to antidepressant therapy.

Either trycyclic and related antidepressants or SSRIs are generally preferred because MAOIs may be less effective and show dangerous interaction with some foods and drugs.

Patient should be reviewed every 1-2 weeks at the start of anideprassant treatment. Treatment should be continued for at least 4 weeks (6 weeks in elderly) before considering whether to switch antidepressant due to lack of efficiency.

Following remission, antidepressant treatment should be continued at the same dose for at least 4-6 months (about 12 months in elderly).

Failure to respond to an initial course of antidepressant, may be necessitate an increase in the dose, switching to a different antidepressant class, or in patient with ‘atypical’ major depression, the use of a MAOIs. Failure to respond to a second antidepressant may require the addition of an augmenting drug such as lithium or liothyronine.

Tricyclic and related antidepressant drugs

This section covers tricyclic antidepressants(TCA) and also 1-, 2-, and 4-ring structured drugs with broadly similar properties.

These drugs are most effectve for treating moderate to severe endogenous depression associated with psychomotor and psychological changes such as loss of appetite and sleep disturbances; improvement in slepp is usually the first benefit of therapy. Since there may be an interval of 2 weeks before the antidepressant action takes place electroconvulsive treatment may be required in severe depression when delay is hazardous or intolerable.

Some tricyclic antidepressants are also effective in the management of panic disorders as well.

About 10 to 20% of patients fail to respond to tricyclic and related antidepressant drugs and inadequate dosage may be account for some these failures. It is important to use doses that are sufficiently high for effectve treatment but not so high as to cause toxic effects. Low doses should be used for initial treatment in the elderly.

TCA and related antidepressant drugs can be roughly divided into those with additional sedative properties and those which are less so. Agitated and anxious patients tent to respond best to the sedative compounds whereas withdrawn and apathetic patients will often obtain most benefit from the less sedative ones.

Common TCAs are;

1. Amitriptyline Hydrochloride
2. Amoxapine
3. Clomipramine Hydrochloride
4. Dosulepin Hydrochloride
5. Doxepin
6. Imipramine Hydrochloride
7. Lofepramine
8. Nortriprtyline
9. Trimipramine


Related antidepressants are;

1. Maprotiline Hydrochloride
2. Mianserin Hydrochloride
3. Trazodone Hydrochloride

MonoamineOxidase Inhibitirs (MAOIs)

Monoamine oxidase inhibitors are used much less frequently than tricyclic and related antidepressants, or SSRIs and related antidepressants because of the dangers of dietary and drug interactions and the fact that it is easier to prescribe MAOIswhen tricyclic antidepressants have been unsuccessful than vice versa.

Phobic patients and depressed patients with atypical, hypochondriacal, or hysterical features are said to respond best to MAOIs. However, MAOIs should be tried in any patients who are refractory to treatment with other antideoressants as there is occasionally dramatic response.

MAOis inhibits monoamine oxidase, thereby causing an accumulation of amine neurotransmitters. The metabolism of some amine drugs such as interact acting sympathomimetics is also inhibited and their pressor action may be potentiated.

Other antidepressants should notbe started for 2 weeks after treatment with MAOIs has been stopped. Conversely, a MAOIs should not be started for at least 2 weeks after a previous MAOI has been stopped.

Common MAOIs are;

1. Phenelzine
2. Isocarboxazid
3. Tranylcypromine
4. Moclobemide

Selective Serotinin Reuptake Inhibitors (SSRIs)

This is a newer class of antidepressants. SSRIs should be used with caution in patients with epilepsy (avoid if poorly controlled, discontinue if convulsuin develop), concurrent electroconvulsive therapy (prolonged seizures reported with fluoxetin), history of mania, cardiac disease, diabetes mellitus, angle closure glaucoma, concomitant use of drugs that increase risk of bleeding, history ofbleeding disorders 9especially gastrointestinal bleeding), hepatic and renal impairment, pregnancy and breast feeding.

Common SSRIs are;

1. Citalopram
2. Escitalopram
3. Fluoxetin
4. Fluvoxamine maleate
5. Paroxetine
6. Sertraline

Other antidepressant drugs

Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Noradrenergic and specific serotonergic antidepressants (NASSAs)
Norepinephrine (noradrenaline) reuptake inhibitors (NRIs)
Norepinephrine-dopamine reuptake inhibitors (NDRIs)

1. Flupentixol
2. Mirtazapine
3. Reboxetine
4. Tryptophan
5. Venlaflaxine

Mechanisms of actions of antidepressants

Mechanism of actions of antidepressants is based on a theory which explains why depressant occurs. According to the theory, there is a low level of monoamine in the brain in depressed persons. Main monoamines found in the brain are dopamine, noradrenalin and serotonin. Even though there are lots of monoamine found in the brain, these are the main monoamine related to depression.

Therefore any chemical compound which is capable of increasing monoamine level in the brain will be an antidepressant. Followings are the main methods of increasing monoamine in the brain;

1. prevention of reuptake of monoamine into synaptic nerve endings from synaptic cleft (tricyclic antidepressants)
2. prevention of serotonin reuptake into synaptic nerve endings from synaptic cleft (SSRI)
3. prevention of noradrenalin and serotonin reuptake into synaptic nerve endings from synaptic cleft (SNSRI)
4. prevention of noradrenalin and serotonin reuptake into synaptic nerve endings from synaptic cleft and serotonin (5HT2A) receptor antagonists (Nefazodone, Trazodone).
5. prevention of monoamine destruction (MAOI)