ANTIDEPRESSANTS

Affective disorders are a group of psychoses associated with changes of mood, i.e. depression
and mania.

Depression is a common psychiatric disorder but the cause for it is not clear.

Depression could be reactive or endogenous.

Reactive depression is due to stressful and distressing circumstances in life.

Endogenous depression is major depression and results from a biochemical abnormality in

the brain. Deficiency of monoamine (noradrenaline, 5 hydroxytryptamine) activity in the
CNS is thought to be endogenous depression.

Symptoms of depression are:

 Emotional symptoms – sadness, misery, hopelessness, low self-esteem, loss of

interest, and suicidal thoughts. (Nurses have to keep this in mind. Many patients have
committed suicide in the hospital itself).
 Biological symptoms – fatigue, apathy, loss of libido, loss of appetite, loss of
concentration and sleep disturbances.

Bipolar depression is characterized by alternate mania and depression. It is less common and
is associated with a hereditary tendency. Mania can be considered opposite of depression
with elation, over-enthusiasm, over-confidence, and is often associated with irritation and
depression.

Antidepressants are drugs used in the treatment of depression.

Classification

1. Tricyclic antidepressants (TCA) – Imipramine, desipramine, clomipramine,

amitriptyline, notriptyline, doxepin.
2. Selective serotonin reuptake inhibitors (SSRI) – Fluoxetine, fluoxamine, paroxetine,
citalopram, sertraline.
3. Monoamine oxidase (MAO) inhibitors – Phenelzine, tranylcypromine, isocarboxazid,
moclobemide.
4. Atypical antidepressants – Trazodone, nefazodone, venlafaxine bupropion,
mianserine, mirtazapine, reboxetine.

Tricyclic antidepressants (TCA)

1. CNS – In normal subjects, TCA cause dizziness, drowsiness, confusion and difficulty
in thinking. In depressed patients, after 2-3 weeks of treatment, elevation of mood
occurs; the patients show more interest in the surroundings and the sleep pattern
becomes normal.
 Mechanism of action – TCAs block the reuptake of neurotransmitters (noradrenaline
or 5-HT) into the nerve-endings and thereby prolong their action on the receptors.
Thus they potentiate amine neurotransmission in the CNS.
2. CVS – Postural hypotension and tachycardia (due to blockade of α1 adrenergic and
muscarinic receptors.
3. ANS – TCAs have anticholinergic properties and cause dry mouth, blurred vision,
constipation and urinary retention.

Pharmacokinetics

TCAs are rapidly absorbed, extensively protein bound and metabolised in the liver. They
have a long t1/2 and can be given once daily. On long term administration, accumulation can
occur resulting in cumulative toxicity.

Adverse Effects

Sedation, postural hypotension, tachycardia, sweating and anticholinergic side effects like dry
mouth, constipation, blurred vision, and urinary retention are relatively common. TCA may
precipitate convulsions in epileptics, may cause hallucinations, and mania in some patients.
TCAs may also cause weight gain due to increased appetite.

Acute toxicity symptoms are (mimic symptoms of atropine poisoning) delirium, excitement,
hypotension, convulsions, fever, arrhythmias, respiratory depression of coma.

Treatment – Physostigmine is given to overcome atropine–like effects; sodium bicarbonate

for acidosis, phenytoin for seizures and arrhythmias. Other supportive measures like
maintenance of BP, respiration, fluid and electrolyte balance are needed.

Tolerance and Dependence

Tolerance develops gradually to the sedative and anticholinergic effects over 2-3 weeks.
Starting with a low dose and gradually increasing the dose minimises the side effects.

Following long–term treatment, TCAs should be gradually withdrawn, as withdrawal

symptoms like headache, anxiety and chills can occur due to physical dependence.

Selective serotonin reuptake inhibitors (SSRI)

include fluoxetine, fluvoxamine, paroxetine, citalopram, sertraline and venlafaxine.

Antidepressant actions and efficacy of SSRIs are similar to TCAs.

Mechanism of action – SSRIs block the reuptake of serotonin (5 hydroxytryptomine) into the
nerve-endings of the brain. Hence they increase serotonin levels in the synapses. Thus they
correct the monoamine deficiency in these neurons.

SSRIs have the following advantages over TCAs –

 Low cardiovascular side effects

 Anticholinergic side effects are negligible
  Less sedation
 Preferred in elderly because of low anticholinergic side effects (anticholinergic
effects like constipation and urinary retention may be troublesome in the elderly)
 Safer in overdose (this is particularly advantageous in patients with depression
because they may have suicidal tendencies.)
 SSRIs are generally well accepted by patients because of fewer side effects.

Adverse effects to SSRIs include nausea, vomiting, insomnia, anxiety and sexual
dysfunction.

Among the SSRIs, fluoxetine is the commonly used.

MAO Inhibitors

Monoamine oxidase (MAO) is an enzyme which metabolises noradrenaline, serotonine and

dopamine. Drugs which inhibit this enzyme enhance the neuronal levels of noradrenaline,
dopamine and 5-HT in the neurons. Antidepressant actions develop slowly over weeks of
treatment.

Side effects of hypotension, weight gain, restlessness, insomnia (due to CNS stimulation),
anticholinergic effects and rarely liver dysfunction. They interact with many drugs and food.

Because of the side effects and drug interactions, MAO inhibitors are not the preferred
antidepressants.

Atypical antidepressants include trazodone, bupropion, mianserin, nefasodone, mirtazapine.

Advantages

 Fewer side effects – particularly sedation and anticholinergic effects.

 Safer in over dose.
 Effective in patients not responding to TCA.
 Bupropion is useful in depression with anxiety. It is also useful to stop the
cigarette smoking habit along with nicotine patch.

Uses of Antidepressants

1. Endogenous depression – Antidepressants are used over a long period. The response
appears after 2-3 weeks of treatment. The choice of drug depends on the side effects
and patient factors like age. In severe depression with suicidal tendencies,
electroconvulsive therapy is used.
2. Panic attacks – Post-traumatic stress disorders and other anxiety disorders – all
respond to antidepressants (acute episodes of anxiety are known as panic attacks).
3. Obsessive compulsive disorders – SSRIs and clomipramine are effective.
4. Nocturnal eneuresis (Bed wetting) in children may be treated with antidepressants –
only when other measures fail and drugs are needed.
 5. Psychosomatic disorders – Newer antidepressants are tried in fibromyalgia, irritable
bowel syndrome, chronic fatigue, tics, migraine, and sleep apnea.
6. Other indications – Attention deficit hyperactivity disorder, chronic pain and chronic
alcoholism – all these conditions may be associated with depression – antidepressants
are tried in these conditions.
Bipolar mood disorder (manic depressive illness) is characterised by mood swings or
changes there could be periods of elation or depression. Such patients needmood
stabilizers.

Nursing implications

 Many patients in depression have suicidal tendencies. They need to be carefully

monitored.
 Most antidepressants take 2-3 weeks for therapeutic benefit. Patient’s attendants
should be informed of this.
 Most antidepressants cause anticholinergic side effects – these should watched for
and appropriately dealt with.