Antidepressants

The first modern antidepressant medication, imipramine, was marketed in 1958.

This tricyclic compound is a modification of the structure of the antipsychotic
chlorpromazine. The reason imipramine and similar drugs are called tricyclics
(TCAs) is because of the compounds' three-ring chemical structure. Dr. Roland
Kuhn, a Swiss psychiatrist, originally administered imipramine to patients with
schizophrenia and found no clinical efficacy. Astute observation and the
persistence of Dr. Kuhn, who studied the use of imipramine in patients with
depression, quickly led to proving imipramine's efficacy for the treatment of
depression. This success served as the catalyst in the search for additional
antidepressant medications that exhibited improved efficacy and that reduced
side effects. At the same time, advances in the understanding of the role of
serotonin in depression pointed toward a new class of antidepressants, the
selective serotonin reuptake inhibitors (SSRIs).

Indications
The antidepressants have many therapeutic uses, but the primary approved use
is to treat major depression as defined by the DSM-IV-TR .Antidepressants are
also effective for the treatment of a number of other conditions, including the
following:
 Anxiety
 Obsessive-compulsive disorders
 Panic disorders
 Bulimia
 Anorexia nervosa
 Posttraumatic stress disorder
 Bipolar depression
 Social phobia
 Irritable bowel syndrome
 Enuresis
 Neuropathic pain
 Migraine headache Attention-deficit/hyperactivity disorder
 Smoking cessation
 Autism

Biologic Theory
The biologic theory states that depression occurs because of a decreased amount
of or the inadequate function of the catecholamine neurotransmitters
norepinephrine or serotonin. Antidepressant drugs affect the responses of these
neurotransmitters. Presynaptic neurons synthesize these neurotransmitters,
which are incorporated into vesicles. The action of the various antidepressants
causes the vesicles to release their contents into the synapse. After they are
released, neurotransmitters cross the synapse and affect receptors on the
postsynaptic neuron. Most of the neurotransmitters are taken back into the
presynaptic neuron to conserve this valuable resource; then they re enter the
synthesis process and are incorporated into the vesicles for future use. The
cyclic antidepressants partially block the reuptake of norepinephrine and
serotonin. Initially, this results in increased amounts of neurotransmitter in the
synapse, which reduces the number of receptors on the postsynaptic membrane.
This change in receptor density, called downregulation, takes several weeks to
occur, and it is temporarily associated with the antidepressant response
According to the biologic theory, a patient who fails to respond therapeutically
to one antidepressant will respond more favorably to a different antidepressant.
It makes sense to switch to an antidepressant that more specifically affects.

CLASSES OF ANTIDEPRESSANTS
SSRIs (Selective Setotonin reuptake Inhibitor)
Mechanism of Action
Inhibit the reuptake(5-hydroxytryptamine or 5-HT) at the synaptic cleft Initial high levels of serotonin
in the cleft will not only activate post-synaptic receptors, but also stimulate autoreceptors of pre-
synaptic cells thereby transiently decreasing serotonin production. Neurons adapt to the high levels of
serotonin in the cleft and autoreceptors are down regulated thereby not interfering with serotonin
production
Changes in receptor adaptation and signal transduction in animal models occur over several weeks
and it is believed that these effects mediate the effects of antidepressants and explain why SSRIs take
several weeks to take effect

Primary Indication
The primary indication of SSRIs is for the treatment of major depressive disorder (MDD)
All SSRIs are equally effective in treating depression, although they differ enough from one another
that failure to respond to one SSRI doesn't predict failure to a different SSRI.
SSRIs are the safest alternative in depressed patients with cardio-vascular comorbidities

Indications for Specific SSRIs

Fluoxetine is approved by the FDA for treatment of
Acute major depressive disorder (adult and pediatric), recurrent major depressive disorder. bulimia
nervosa, obsessive-compulsive disorder, panic disorder, and premenstrual dysphoric disorder-Also
effective in treating MDD associated with alcoholism,MDD associated with diabetes, seasonal
affective disorder, posttraumatic stress disorder, obesity, hot flashes, migraine headache prophylaxis,
and fibromyalgia.
Paroxetine is approved by the FDA for treatment of:
Acute major depressive disorder (adults), generalized anxiety disorder, and social phobia Also
effective in treatment of interferon-induced major depressive disorder, diabetic neuropathy, premature
ejaculation, and vasovagal syncope
Sertraline is approved by the FDA for treatment of:
Acute major depressive disorder (adults), recurrent major depressive disorder, obsessive-compulsive
disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and social
anxiety disorder
Also effective in treating major depressive disorder associated with myocardial infarction, major
depressive disorder associated with Alzheimer's dementia, generalized anxiety disorder, premature
ejaculation, and dysthymic disorder
Fluvoxamine is approved by the FDA for treatment of:
Obsessive-compulsive disorder (adult and pediatric)
Citalopram is approved by the FDA for treatment of:
Acute major depressive disorder (adults) Also effective in the treatment of panic disorder,
prostatodynia, and social anxiety disorder, MDD associated with stroke, diabetic neuropathy,
dysthymic disorder, headache, impulsive aggressive disorder, obsessive compulsive disorder, panic
disorder, pathologic crying, pathologic gambling, posttraumatic stress disorder, and premenstrual
dysphoria syndrome
Escitalopram is approved by the FDA for treatment of.
Acute major depressive disorder (adults) and generalized anxiety disorder

Adverse Effects
 Gastrointestinal GI: Side effects are common, including nausea, cramping, diarrhoea,
bloating, and abdominal pain.
 Cardiovascular: May cause bradycardia, normalization of heart rate variability, which may
be cardio-protective. Sertraline is extensively studied (SADHEART trial, Glassman et al.,
JAMA, 2002), proven effective post- myocardial infarction and with unstable angina, with no
adverse cardiac effects.
 Hematologic: Decrease platelet aggregation, increase bleeding time, leading to easy bruising
and risk for GI and other bleeding, particularly in the elderly and when combined with non-
steroidal anti-inflammatory drugs (NSAIDS).
 Hepatic: Mild AST, ALT elevations possible.
 Metabolic and Endocrine: In women, galactorrhea may occur with some SSRIs, due to
serotonin down-regulation of dopamine.
 Sexual Dysfunction: Decreased libido and delayed or no orgasm are the most common.
Dysfunction of erection or engorgement less common.
 Neurologic and Neuropsychiatric : SSRIs can cause neuromuscular irritability and
extrapyramidal side effects. including worsening of tremor and rigidity in disorders such as
Parkinson's Disease and spastic cerebral palsy. Serotonin Syndrome, caused by excessive
serotonin (such as occurs with high-dose SSRIs or SSRIs in combination with MAOIS and
other agents that potentiate serotonin function), is characterized by delirium, neuromuscular
irritability, seizures and autonomic instability signs. It is clinically similar to NMS. Apathy or
blunting of emotions is also common with long-term SSRI treatment, thought to be secondary
to dopamine down-regulation with SSRIs.
 Pregnancy and Lactation: (see section on Women's Mental Health and Reproductive
Psychiatry), SSRIs are all Pregnancy class C medications. Recent evidence suggests risk for
persistent pulmonary hypertension in neonates when mothers treated in third trimester with
SSRIs. Paroxetine recently implicated in an increased risk of birth defects, particularly VSDs
and ASDs. SSRIs may cause discontinuation symptoms in neonates. SSRIs all pass into breast
milk, though levels of sertraline in nursing infants minimal.
 Overdose: Generally safe in overdose.
 Suicide Risk: SSRIs now carry "black box" warnings due to increased risk of suicidality
(suicidal thinking and behavior) in children and adolescents being treated with these agents.
An FDA review of a total of 24 antidepressant trials involving over 4400 patients showed a
greater risk of suicidality during the first months of treatment in those receiving
antidepressants. The average risk of such events on drug was 4%, twice the placebo risk of
2%. Other relevant recommendations from the FDA include:
o Anyone considering the use of an antidepressant in a child or adolescent for any
clinical use must balance the risk of increased suicidality with the clinical need
Patients who are started on therapy should be observed closely for clinical worsening,
suicidality, or unusual changes in behavior
o Families and caregivers should be advised to closely observe the patient and to
communicate with the prescriber

TCAs (Tricyclic Acids)

Mechanism of Action
  TCAs block the Norepinephrine and 5-HT presynaptic transporter sites and to a lesser extent
the Dopamine reuptake transporter
 Clomipramine is predominantly a 5-HT reuptake inhibitor, whereas desipramine,
nortriptyline, and protriptyline are predominantly NE reuptake inhibitors and amitriptyline,
doxepin, imipramine, and trimipramine are largely equal in inhibiting both the NE and the 5-
HT reuptake mechanism

Indications
The primary indication of TCAs, except clomipramine, is for the treatment of Major Depressive
Disorder Clomipramine is FDA approved for the treatment of obsessive-compulsive disorder

Special Indications
 Panic disorder, social phobias, post traumatic stress disorder, reducing binging and purging in
bulimia nervosa, refractory pain syndromes (diabetic neuropathy, fibromyalgia, fibrositis,
rheumatoid arthritis, central pain)
 Effective in the treatment of premature ejaculation Imipramine and clomipramine are
effective in treating catapleptic episodes associated with narcolepsy

Adverse Effects
 Anticholinergic: Blurred vision, urinary retention, constipation, dry mouth are not dose
dependent. The estimation of anticholinergic potency are as follows: amitryptyline>
trimipramine > doxepin > imipramine > desipramine > nortriptyline.
 Cardiovascular: Orthostatic hypotension is the most serious complication, due to anti a-1
adrenergic effects. TCAs are class (quinidine-like) antiarrhythmics, causing decreased
conduction through the A-V node and resulting in Q-T prologation.
 In patients with preexisting first degree atrioventricular (AV) block there is a risk of complete
block and therefore ECG monitoring is required in this patient population
 TCAS should not be used in patients with cardiovascular disease and should be avoided in
post-MI patients in whom TCAs are associated with increased risk of morbidity and mortality
 Dermatologic: Cutaneous vasculitis, urticaria, and photosensitivity.
 Hematologic: Benign eosinophilia and leucopenia transiently occur in the first few weeks of
therapy. Agranulocytosis, although rare, is amedical emergency and can be fatal so CBC
should bemonitored in this patient group.
 Hepatic: AST, ALT, Alk Phos, or even bilirubin elevations are not uncommon. AST or ALT
elevation with values three times the upper limit of normal are worrisome and the TCA
should be discontinued. and Endocrine: In women, Galactorrhea and amenorrhea, which are
dose dependent, have been reported. Weight gain has also been reported with TCAs.
 Neurologic and Psychiatric: Acute delirium, as a result of TCA's anticholinergic properties,
has been reported and can be treated with physostigmine. This effect is more common in the
elderly and African Americans and is dose dependent (more common in higher doses). A fine
resting tremor has also been observed. TCA's can lower the seizure threshold. Switching from
depressed to manic or hypomanic states has been reported in bipolar depressed patients.
 Sexual Dysfunction: Primarily erectile dysfunction. Imipramine > desipramine >
clomipramine > amitriptyline> protriptyline in descending order, cause disturbances in sexual
function.
 Pregnancy and Lactation: amitriptyline, nortriptyline associated with congenital anomalies
(category D).
  Overdose: The most serious consequence of TCA overdose relate to their cardiovascular
effects. Superventricular tachycardia, multifocal PVCs, ventricular tachycardia, flutter, or
fibrillation can result in severe hypotension or shock. ECG abnormalities in overdose include
prolonged PR interval, widened QRS complex, QT prologation, T-wave flattening or
inversion, ST-segment depression, right bindle branch block, complete heart block, or cardiac
standstill. Treatment for overdose includes alkalization of serum in addition to
cardiacmonitoring and ventilatory and pressor support. The combined use of TCA and
MAOIS is contraindicated

SNRIs (Serotonin Nor-Epinephrine Reuptake Inhibitor)

Mechanism of Action
SNRIs block monoamine transporters more selectively than TCAs and without the potential adverse
cardiac-conduction effects of TCAS
Duloxetine and Venlafaxine block both serotonin and norepinephrine reuptake. At lower dosages
(i.e.. <200mg/day) Venlafaxine appears to be more selective for serotonin transporter; at higher
dosages, the noradrenergic effects become more prominent

Indications
In some studies, Venlafaxine appears to demonstrate superior efficacy and higher rates of remission in
severe depression as compared to SSRIs such as fluoxetine or TCAs. This is still an open issue
Venlafaxine and duloxetine are effective for the treatment of chronic pain, diabetic neuropathy, and
pain occurring as part of primary or secondary depression. Only Duloxetine has FDA approval for
diabetic peripheral neuropathy

Adverse Effects
Generally, side effects are similar to those associated with SSRIS. Dose dependent increases in
systolic and diastolic blood pressure have been reported in patients on venlafaxine, and bupropion

MAOIS (Monoamine Oxidase Inhibitor)

Mechanism of Action
MAOIS inhibit the activity of monoamine oxidase. an enzyme that breaks down catecholamine and
indolamine neurotransmitters, thereby increasing levels of norepinephrine, dopamine, and serotonin
neurotransmitters
Earlier MAOIs inhibited monoamine oxidase inversibly but newer MAOIs such as moclobemide are
reversible inhibitors

Indications
MAOIs are indicated for typical Major Depressive Disorder and atypical depression. They are
preferentially more effective than TCAs in the treatment of atypical depression
Special Indications
Panic disorder, social phobia, neurodermatitis, treatment resistant narcolepsy, migrane headaches. and
idiopathic hypotension

Adverse Effects
 Allergic: Maculopapular rashes, red-green blindness with optic atrophy (rare).
 Cardiovascular: Conduction abnormalities such as QTc Interval prolongation, orthostatic
hypotension.
 Hypertensive Crisis: The consumption of foods or other products containing pressor amines
or sympathomemetic agents together with MAOIS have resulted in critical hyperadrenergic
states characterized by elevations in both systolic and diastolic blood pressures with
potentially dire consequences such as fatal strokes, cardiac arrhythmias, or cardiac failure.
Tyramine containing foods, most commonly aged cheeses and red wine, are frequently
implicated in this complication. Other amines or precursors to amines such as histamine,
dopamine, levodopa, and tyrosine may also be implicated. Sympathomimetics such as
amphetamines and ephedrine and TCAs can also precipitate this complication when used in
conjunction with MAOIS.
 Patients on MAOIS should therefore be on tyramine- restricted diets and avoid over the
counter remedies that may contain sympathomimetics such as phenylephrine based cold
remedies. In addition, a washout of at least 14 days should be in effect when switching from
MAOIS to other antidepressants to prevent potential hypertensive crisis or serotonin
syndrome
 Neurologic: Peripheral sensory neuropathy-probably as a result of pyridoxine 534deficiency
secondary to phenelzine. Other effects include ataxia, hyperacusis, muscle tension, myoclonic
jerks, carple tunnel syndrome, and in its most severe form seizures, coma, or death.
Anorgasmia and impotence have been reported with phenelzine. Phenelzine and
tranylcypromine have been associated with daytime drowsiness. Psychiatric: Similar to TCAs
"flipping" from depression to mania or hypomania can occur with MAOIS.
 Overdose: Potentially fatal, symptoms may not be evident for 6 to 12 hrs. after ingestion.
These include flushing, diaphoresis, tachycardia, hypertension, mental confusion, increased
deep tendon reflexes, involuntary movements, seizure.
 Teratogenicity and Excretion in Breast Milk: FDA category ,MAOIS are contraindicated
during pregnancy and tranylcypromine is known to be excreted in breast milk.

Atypical antidepressants
Mechanism of action
Same as Tricyclics. Nor-Epinephrine ,5HT, Dopamine Blocking reuptake so that there will be
increase in receptor site.

Indication
Bupropion is associated with less nausea, diarrhoea, somnolence and sexual dysfunction than SSRIs.
Bupropion is also effective in treating SSRI -induced sexual dysfunction.

Adverse effects
Bupropion has been documented to cause seizures at doses >400mg/day. It should not be used in
patients with epilepsy.
 Role of a nurse in Administration of Anti Depressants
Nursing Interventions to the related Side Effects
SAFETY ISSUES NURSING INTERVENTIONS
Drug interactions (multiple, as Instruct clients to inform their physician or nurse practitioner of all
discussed in the text) medications they are taking, including herbal preparations, over-the-
counter drugs, and any medications they have stopped taking within
the previous 2 weeks.
Notify the physician immediately when any symptoms of serotonin
syndrome are assessed. Do not administer the offending agent.
 Monitor vital signs.
 Protect from injury secondary to muscle rigidity or change in
mental status.
 Provide cooling blankets for temperature regulation.
 Monitor intake and output.
The condition usually resolves when the offending agent is promptly
discontinued but can be fatal without intervention
Increased risk for suicide Assess frequently for presence or worsening of suicide ideation,
 Initiate suicide precautions as needed.
Monitor clients use of medication as prescribed, since these
medications can be lethal in overdose.
Sedation instruct clients not to drive or operate dangerous machinery when
experiencing sedation.
Discontinuation syndrome: Instruct clients that all antidepressants have some potential for
SSRIs-dizziness, lethargy, discontinuation syndrome and should not be stopped abruptly but
headache, nausea rather tapered off
TCAS-hypomania, akathisia,
cardiac arrhythmias,
gastrointestinal upset, panic attacks
MAOIS-flu-like symptoms,
confusion, hypomania
Photosensitivity Instruct clients of their vulnerability to severe sunburn and recommend
sunscreen.
Orthostatic hypotension (TCAs) Instruct clients to rise slowly from sitting to standing.
Monitor blood pressure to assess for symptoms.
Tachycardia, arrhythmias (TCAs) Monitor vital signs, especially in elderly with preexisting
cardiovascular disorders.
Hyponatremia (SSRIs) especially Instruct clients to report any symptoms of nausea, malaise, lethargy,
among the elderly (potentially life muscle cramps.
threatening) Assess for disorientation or restlessness.
Monitor sodium levels:
 <120 mEq/L risk for seizure, coma, respiratory arrest
 Withhold medication, contact physician, restrict water intake
Blurred vision (TCAs and Instruct clients to avoid driving, and reassure them that this side effect
atypicals) usually resolves within 3 weeks. Monitor blood pressure to rule out
symptoms of hypertension.
Constipation Recommend a high-fiber diet and regular exercise, and instruct clients
to report any symptoms of ongoing difficulty with bowel movements.

Client and Family Education Related to Antidepressant

The client should:

 Continue to take the medication even though symptoms have not subsided. The therapeutic
effect may not be seen for as long as 4 weeks. If after this length of time no improvement is
noted, the physician may prescribe a different medication.
 Use caution when driving or operating dangerous machinery. Drowsiness and dizziness can
occur. If these side effects become persistent or interfere with ADLs, the client should report
them to the physician. Dosage adjustment may be necessary.
 Not discontinue use of the drug abruptly. To do so might produce withdrawal symptoms, such
as nausea, vertigo, insomnia, headache, malaise, nightmares, and return of symptoms for
which the medication was prescribed.
 Use sunblock lotion and wear protective clothing when spending time outdoors. The skin may
be sensitive to sunburn.
 Report occurrence of any of the following symptoms to the physician immediately: sore
throat, fever, malaise, yellowish skin, unusual bleeding, easy bruising, persistent
nausea/vomiting, severe headache, rapid heart rate, difficulty urinating, anorexia/weight loss,
seizure activity, stiff or sore neck, and chest pain.
 Rise slowly from a sitting or lying position to prevent a sudden drop in blood pressure.
 Take frequent sips of water, chew sugarless gum, or suck on hard candy if dry mouth is a
problem. Good oral care (frequent brushing and flossing) is very important.
 Not consume the following foods or medications while taking MAOIS: aged cheese, wine
(especially Chianti), beer, chocolate, colas, coffee, tea, sour cream, smoked and processed
meats, beef or chicken liver, canned figs, soy sauce, overripe and fermented foods, pickled
herring, raisins, caviar, yogurt, yeast products, broad beans, cold remedies, diet pills. To do so
could cause a hypertensive crisis. life-threatening
 Avoid smoking while receiving tricyclic therapy. Smoking increases the metabolism of
tricyclics, requiring an adjustment in dosage to achieve the therapeutic effect.
 Avoid drinking alcohol while taking antidepressant therapy. These drugs potentiate the effects
of each other.
 Avoid use of other medications (including over- the-counter medications) without physician's
approval while receiving antidepressant therapy. Many medications contain substances that
could precipitate a life-threatening hypertensive crisis in com- bination with antidepressant
medication.
 Notify physician immediately if inappropriate or prolonged penile erections occur while
taking trazodone. If the erection persists longer than 1 hour, seek emergency department
treatment. This condition is rare but has occurred in some men who have taken trazodone. If
measures are not instituted immediately, impotence can result.
 Not "double up" on medication if a dose of bupropion (Wellbutrin) is missed unless advised
to do so by the physician. Taking bupropion in divided doses will decrease the risk of seizures
and other adverse effects. Follow the correct procedure for applying the selegiline transdermal
patch:
 Apply to dry, intact skin on upper torso, upper thigh, or outer surface of
upper arm.
 Apply approximately same time each day to new spot on skin after removing
and discarding old patch.
 Wash hands after applying the patch.
 Avoid exposing application site to direct heat re (e.g., heating pads, electric
blankets, heat lamps, b hot tub, or prolonged direct sunlight).
 If patch falls off, apply new patch to a new site and resume previous
schedule.
 Be aware of possible risks of taking antidepressants during pregnancy. Safe use during
pregnancy and lactation has not been fully established. These drugs are believed to readily
cross the placental barrier; if so, the fetus could experience adverse effects of the drug. Inform
the physician immediately if pregnancy occurs, is suspected, or is planned.
 Be aware of the side effects of antidepressants. Refer to written materials furnished by health-
care providers for safe self-administration.
 Carry a card or other identification at all times describing the medications being taken.
BIBLIOGRAPHY
1. Morgan Karyn I. Townsend Mary C. Psychiatric Mental Health Nursing: Concept of care in
evidence-based Practice. 9th edition .New Delhi. F.A. Davis. 2022
2. Kumar C.L. Subhash Indra. A textbook of Psychiatry and Mental Health Nursing:
New Delhi. EMESS. 2025. 214-20
3. Ahuja niraj. A short textbook of Psychiatry. 7th edition, New Delhi. JAYpee.2016
4. Varcolis E M. Essentials of Psychiatric Mntal Health nursing: a communicaton
approach to Evidence based Care. Second Edition. China. ELSEVIER. 58-60

JOURNAL REFERENCE
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