ANTIDEPRESSANTS

Mr. Shridhar malagi

MSc(n)1st year
KAHER INS ,Belagavi
Depression
• Depression is an affective disorder characterized by a persistent and
intense feeling of sadness much more severe and longer lasting than
the suspected precipitating event. There may be no external causes
• Individuals with depression have little energy, disturbed sleep patterns,
loss of appetite, and absence of motivation to perform
activities of daily living. They describe overwhelming feelings of
sadness, despair, hopelessness, and disorganization.
Cont..
• It can interfere with a person’s life, his family, job, and social
relationships. It can lead to multiple physical problems that further
depression and increase risk of suicide.
• Researches about drugs that can effectively relieve depression lead to
the formulation of biogenic amine theory which states that depression
results from a deficiency of biogenic amines (NE, dopamine, and 5-
HT) in key areas of the brain that regulate arousal, alertness, attention,
moods, appetite, and sensory processing.
Antidepressants
• Antidepressants are used to alter the concentration of
neurotransmitters in the brain that is responsible for the
depressed affect (feelings in response to the environment, whether
positive and pleasant or negative and unpleasant).
These drugs counteract the effects of
neurotransmitter deficiencies in three ways:
• Inhibit the effects of monoamine oxidase (MAO) resulting to
increased norepinephrine and serotonin or 5-hydroxytryptamine (5-
HT) in the synaptic cleft;
• Block the reuptake function of the synaptic cleft resulting to increased
neurotransmitter levels in the synaptic cleft; and
• Regulate receptor sites and breakdown of neurotransmitters resulting
in accumulation of neurotransmitter in the synaptic cleft
Antidepressants are classified into three
groups:
Tricyclic antidepressants (tcas)
Monoamine oxidase inhibitors (maois)
Selective serotonin reuptake inhibitors (ssris).
 Tricyclic Antidepressants
Amines
• amitriptyline
• amoxapine (Asendin)
• clomipramine (Anafranil)
• doxepin (Sinequan)
• imipramine (Tofranil)
Secondary Amines
• despiramine (Norpramin)
• nortriptyline (Aventyl)
• protriptyline (Vivactil)
• tetracyclic (Maprotiline)
Monoamine Oxidase Inhibitors (MAOI)
• isocarboxazid (Marplan)
• phenelzine (Nardil)
• tranylcypromine (Parnate)
Selective Serotonin Reuptake Inhibitors (SSRI)
• citalopram (Celexa)
• escitalopram (Lexapro)
• fluoxetine (Prozac)
• fluvoxamine (Luvox)
• paroxetine (Paxil)
• sertraline (Zoloft)
Tricyclic Antidepressants (TCAs)

Has three sub-class namely: amines, secondary amines, and tetracyclics

Primarily reduce the uptake of 5HT and NE into nerves
The choice of TCA depends on individual response and tolerance to the drug.
Therapeutic Action

• By inhibiting presynaptic reuptake of NE and 5-HT, there will be an accumulation

of these neurotransmitters in the synaptic cleft which will increase the stimulation
of the postsynaptic receptors.
Indications

• Primarily indicated for the relief of symptoms of depression, particularly anxiety

and sleep disturbances.
• Some TCAs are indicated for enuresis in children older than 6 years.
• TCAs also act as anticholinergic.
• Clomipramine is approved for use in treatment of obsessive-compulsive disorders
(OCDs).
Pharmacokinetics

Antidepressants are highly lipophilic and protein-bound. The half-life is long and
usually more than 24 hours. It is predominantly metabolized in the liver.

Route Onset Peak Duration

Oral Varies 2-4 h –

Half-life (T1/2) Metabolism Excretion

8-16 h liver urine
 Contraindications
 Allergy to TCAs. Prevent severe hypersensitivity reactions.
 Myocardial infarction. Can reoccur because of the cardiac effects of the
drug
 Myelography within previous 24 hours or in the next 48 hours. Prevent
possible drug-drug interaction with dyes
 Concurrent use of MAOIs. Potential for serious adverse effects or toxic
reactions
 Pregnancy, lactation. Potential adverse effects to the fetus and the baby
 Preexisting cardiovascular disorders. Drug has cardiac stimulatory effect
 Angle-closure glaucoma, urinary retention, prostate hypertrophy,
GI or GU surgery. Exacerbated by the anticholinergic effects of the
drug
 History of seizures. Seizure threshold is decreased because of
stimulation of receptor sites
 Hepatorenal diseases. Interfere with drug metabolism and excretion
which increase the risk of drug toxicity
Adverse Effects

1. CV: orthostatic hypotension, hypertension, arrhythmias, palpitations,

myocardial infarction, angina, stroke
2. GI: dry mouth, constipation, nausea, vomiting, anorexia, increased salivation,
cramps, diarrhoea
3. GU: urinary retention and hesitancy, loss of libido, changes in sexual
functioning
4. Miscellaneous: alopecia, weight gain or loss, flushing, chills, nasal congestion
5. Abrupt cessation causes withdrawal syndrome characterized by nausea,
headache, vertigo, malaise, and nightmares.
Monoamine Oxidase Inhibitors (MAOIs)

• Monoamine oxidase (MAO) is an enzyme found in nerves and other

tissues. MAOIs exert their effect in relieving depression by inhibiting
this enzyme to break down the biogenic amines NE, dopamine, and 5-
HT.
• Now used rarely because of their strict and specific dietary regimen to
prevent toxicity. However, there are patients who respond only to
MAOIs and so these remain to be available.
Therapeutic Action

• By blocking the breakdown of the biogenic amines, these drugs pave

way for the accumulation of NE, dopamine, and 5-HT in the neuronal
storage vesicles to cause increased stimulation of the postsynaptic
receptors. This increased stimulation is thought to be the reason for the
relief of depression.
 Indications
• MAOIs are generally indicated for patients who do not respond to other safer antidepressants.
 Children
 Avoided in children if at all possible because of the potential for drug-food interactions and serious adverse
effects.
 Adults
 Adults must be educated that effects of drug therapy may not be seen for 4 weeks.
 Also, the cause of depression must be ruled out before therapy begins.
 Use cautiously for pregnant and lactating women because of potential adverse effects to fetus and baby.
 Older adults
 Older adults more susceptible to the adverse effects of the drugs and from CNS effects (e.g. increased
sedation, dizziness, etc.)
 Doses of these drugs need to be reduced and careful monitoring for drug toxicity is a must, especially for
those who have hepatic and renal impairment.
Pharmacokinetics

Route Onset Peak Duration

Oral Slow – 48-96 h

Half-life (T1/2) Metabolism Excretion Half-life (T1/2)

unknown liver urine unknown
 Contraindications and Cautions
• Allergy to MAOIs. Prevent severe hypersensitivity reactions.
• Pheochromocytoma. Sudden increase in NE can lead to severe hypertension and CV emergencies
• CV diseases (hypertension, coronary artery disease, angina, congestive heart failure). Exacerbated
by increased NE levels
• History of headaches.
• Abnormal CNS vessels or defects. Potential increase in blood pressure and vasoconstriction associated
with higher NE levels can precipitate a stroke
• Myelography within previous 24 hours or in the next 48 hours. Prevent possible drug-drug
interaction with dyes
• Pregnancy, lactation. Potential adverse effects to the fetus and the baby
• Hepatorenal diseases. Interfere with drug metabolism and excretion which increase the risk of drug
toxicity
Adverse Effects

• CNS: dizziness, excitement, nervousness, mania, hyperreflexia, tremors,

confusion, insomnia, agitation, blurred vision
• CV: orthostatic hypotension, arrhythmias, palpitations, angina, potentially fatal
hypertensive crisis (occipital headache, palpitations, neck stiffness, nausea,
vomiting, sweating, dilated pupils, photophobia, tachycardia, chest pain)
• GI: liver toxicity, nausea, vomiting, diarrhea or constipation, anorexia, weight
gain, dry mouth, abdominal pain
• GU: urinary retention, dysuria, incontinence, changes in sexual function
Selective Serotonin Reuptake Inhibitors (SSRIs)

• SSRIs is the newest group of antidepressants available in the market.

• Only has blocking effect on the reuptake of 5-HT and has little to no
effect on NE.
• Have lesser adverse effects compared to TCAs and MAOIs. This
makes them a better choice for many patients.
Therapeutic Action

• Blocks the reuptake of 5-HT and therefore increases its level in the
synaptic cleft.
• Realization of full therapeutic effect is up to 4 weeks.
Indications

• Indicated for treatment of depression

• OCD
• Panic attacks
• Bulimia
• Premenstrual dysphoric disorder (PMDD)
• Social phobias
• Social anxiety disorders.
Children
• Can cause serious adverse effects on children.
• Only fluvoxamine and sertraline have established pediatric dosage guidelines for treatment of
OCDs.
• Fluoxetine is widely used to treat depression in adolescents.
Adults
• Must be educated that effects of drug therapy may not be seen for 4 weeks.
Also, the cause of depression must be ruled out before therapy begins.
• Use cautiously for pregnant and lactating women because of potential adverse effects to fetus and
baby.
Older adults
• More susceptible to the adverse effects of the drugs and from CNS effects (e.g. increased sedation,
dizziness, etc.)
• Doses of these drugs need to be reduced and careful monitoring for drug toxicity is a must,
especially for those who have hepatic and renal impairment
Pharmacokinetics

Route Onset Peak Duration

Oral Slow 6-8 h –

Half-life (T1/2) Metabolism Excretion Half-life (T1/2)

2-4 weeks liver urine, feces 2-4 weeks
Contraindications and Cautions

• Allergy to SSRIs. Prevent severe hypersensitivity reactions.

• Hepatorenal diseases. Interfere with drug metabolism and excretion
which increase the risk of drug toxicity
• Severely depressed, suicidal patients. Risk of increased suicidality
• Pregnancy, lactation. Potential adverse effects to the fetus and the
baby
Adverse Effects

• CNS: headache, drowsiness, dizziness, insomnia, anxiety, tremor, agitation,

seizures
• Respiratory: cough, dyspnea, upper respiratory infections, pharyngitis
• GI: nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, changes in taste
• GU: painful menstruation, cystitis, sexual dysfunction, urgency, impotence
• Miscellaneous: sweating, rash, fever, pruritus
Nurse's Responsibility for a Patient Receiving
Antidepressants
• Most of the nurse's responsibilities for a patient on antidepressants are
the same as for a patient receiving antipsychotics.
In addition:
• Patients on MAOIs should be warned against the danger of ingesting
tyramine-rich foods which can result in hypertensive crisis.
• Some of these foods are beef liver, chicken liver, fermented sausages,
dried fish, over riped fruits, chocolate and beverages like wine, beer
and coffee.
Cont..
• Report promptly if occipital headache, nausea, Vomiting, chest pain or
other unusual symptoms occur; these can herald the onset of
hypertensive crisis.
• Instruct the patient not to take any medication without prescription.
• Caution the patient to change his position slowly to minimize
orthostatic hypotension.
• Strict monitoring of vitals, especially blood pressure is essential.