Anti-depressant drugs

Samra Bashir
 Learning Objectives
1. Classify the drugs used in the treatment of depression,
providing examples of each.
2. Describe the pharmacological actions, clinical efficacy and
side/ adverse effects of antidepressant drugs.
 Depression
Definition:
Mood state, as indicated by feelings of sadness, despair, anxiety,
emptiness, discouragement, or hopelessness; having no feelings;
or appearing tearful.
 Depression
Classification:
• Major depressive disorder (unipolar major depression)
• Persistent depressive disorder (dysthymia)
• Disruptive mood dysregulation disorder
• Premenstrual dysphoric disorder
• Substance/medication induced depressive disorder
• Depressive disorder due to another medical condition.                                  
• Other specified depressive disorder (eg, minor depression)
• Unspecified depressive disorder
 Major depressive disorder
(Unipolar major depression)
Major depressive disorder (MDD) is characterized by
• Depressed mood most of the time for at least 2 weeks and/or loss of interest or pleasure in most or all
activities
Accompanied by:
• experiencing fatigue
• having trouble sleeping — insomnia — or sleeping too much
• feeling worthless or guilty
• having difficulty concentrating and making decisions
• unintentionally losing or gaining a significant amount of weight
• experiencing a type of restlessness called psychomotor agitation or finding it difficult to think, speak, and
do other everyday things, called psychomotor impairment
• having frequent thoughts of death
• MDD is associated with substantial morbidity and mortality
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5),
• 70% of patients have response to drugs. American Psychiatric Association, Arlington, VA 2013.
 Pathophysiology of MDD
• Monoamine hypothesis of depression: depression is related to a
deficiency in the amount or function of cortical and
limbic serotonin (5-HT), Norepineprhine and dopamine
(monoamines)
• The level of a amine neurotransmitters can be influenced by
physical illness, genetics, substance abuse, diet, hormonal
changes, brain injury or social circumstances
Limitations to theory –
• despite antidepressant medications approximately 33% of patients
with MDD (major depressive disorder) remain refractory to first
line agents
• Many studies have not found an alteration in function or levels of
monoamines in depressed patients.
• In addition, some candidate antidepressant agents under study do
not act directly on the monoamine system.
 Pathophysiology of MDD
Neurotropic hypothesis of depression
• A drop in the levels of nerve growth factors/neurotrophic factors especially
Brain-derived neurotrophic factor(BDNF) is responsible for the development
of depression.
• BDNF are critical in the regulation of neural plasticity, resilience, and
neurogenesis.
• Animal and human studies indicate that stress and pain are associated with a
drop in BDNF levels resulting in atrophic structural changes in the
hippocampus and perhaps other areas such as the medial frontal cortex and
anterior cingulate.
• Depression and chronic stress states have also been associated with a
substantial loss of volume in the anterior cingulate and medial orbital frontal
cortex which appears to increase as a function of the duration of illness and
the amount of time that the depression remains untreated.
• Administration of antidepressants increases BDNF levels in clinical trials and
may be associated with an increase in hippocampus volume in some
patients.
 Why to treat depression?
• Prevalence of depression is quite high in both developing and developed
world (lifetime prevalence 15%).
• Depression is one of the most common cause of disability.
• Major depression (MDD) is associated with substantial morbidity and
mortality.
• Medical conditions—from chronic pain to coronary artery disease are
found as associated with MDD.
• When depression coexists with other medical conditions, the patient’s
disease burden increases, and the quality of life—and often the prognosis
for effective treatment—decreases significantly.
 Therapeutic uses of antidepressants
• Antidepressants have received US Food and Drug Administration (FDA) approvals for the
treatment of
• Major depressive disorder (primary indication)
• panic disorder,
• generalized anxiety disorder (GAD),
• post-traumatic stress disorder (PTSD), and
• obsessive-compulsive disorder (OCD).
• In addition, antidepressants are commonly used to treat pain disorders such as neuropathic
pain and the pain associated with fibromyalgia.
• Some antidepressants are used for treating premenstrual dysphoric disorder (PMDD),
mitigating the vasomotor symptoms of menopause, and treating stress urinary incontinence.
General mechanism of antidepressant drugs
 Classification of antidepressant drugs
• Selective Serotonin Reuptake Inhibitors (SSRIs)
 (Fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine)
• Serotonin-Norepinephrine Reuptake Inhibitors
• Selective Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) – Venlafaxine,
desvenlafaxine, duloxetine, milnacipran and levomilnacipran
• Tricyclic antidepressants (TCAs) -  Amitryptyline, imipramine, desipramine, doxepin
• 5-HT2 Antagonists – trazodone, nefazodone and vortioxetine
• Tetracyclic and unicyclic antidepressants
Maprotiline, bupropion, mirtazapine, amoxapine, vilazodone
• Monoamine Oxidase Inhibitors phenelzine, tranylcypromine, selegiline
Mechanism
of action
Enhanced
MAOIs
monoamine
neurotransmission

SSRIs
SNRIs
TCAs (+
5 HT2 antihistamine,
α-adrenergic
antagonists blocking, and
anticholinergic)
 SSRIs
(Fluoxetine (protoptype) , sertraline, citalopram, escitalopram, fluvoxamine, paroxetine,)
Mechanism Block the reuptake
of action of serotonin,
increasing its
concentration in
synaptic cleft and
its postsynaptic
neuronal activity

SSRIs

The SSRIs do not

bind aggressively to
histamine,
muscarinic, or other
receptors and are
more potent in
inhibiting SERT than
NET
 SSRIs
Pharmacokinetics
• All of the SSRIs well absorbed orally, peak levels are seen in 2-8 hrs
• Food has little effect on absorption, except for sertraline, food increases its absorption
• Half life = 16-36 hrs, allowing single daily dose. SSRIs are metabolized in the liver and
metabolites are excreted through kidneys.
• However, in the case of fluoxetine, the elimination half-life of its active metabolite
norfluoxetine, is about three times longer than fluoxetine.
• As a result, fluoxetine has to be discontinued 4 weeks or longer before an MAOI can be
administered to mitigate the risk of serotonin syndrome.
• Fluoxetine is available as sustained release formulation allowing once weekly dose.
• Dosage of SSRIs should be reduced in patients with hepatic function impairment.
 SSRIs
Adverse effects (result from increased serotonergic activity due to potent SERT inhibition)
• Gastrointestinal: nausea, GI upset, constipation, diarrhea, and other GI symptoms
• Diminished sexual functions and interest – 17% (most prominently with paroxetine)
• Weight gain particularly with paroxetine (6%)
• Dry mouth
• CNS: Headaches, insomnia or hypersomnia, anxiety, dizziness
• Rash or itching – 6%
• Tremor
• QT interval prolongation with citalopram
• Serotonin withdrawal syndrome - Abrupt discontinuation of SSRIs may precipitate dysphoria,
dizziness, gastrointestinal distress, fatigue, chills, and myalgias. This syndrome is more common
with paroxetine and fluvoxamine (short half-lives), and less common in fluoxetine (long half life)
• Teratogenic effect: Most antidepressants by FDA are category C agents. Paroxetine may cause
cardiac septal defects in first trimester exposures. Thus, it is classified as category D agent.
 SSRIs
• Suicidal ideation especially in children
• Serotonin syndrome: All the SSRIs have a potential to cause serotonin syndrome with
combined with MAOIs. So use of SSRIs with MAOIs is contraindicated.
• Serotonin syndrome is a fatal condition resulting from excessive serotonergic
activity
• The associated symptoms are:
• Cognitive changes (e.g; confusion)
• Behavioral changes (e.g; agitation or restlessness)
• Hyperreflexia
• and/or autonomic manifestation such as fever, shivering, diaphoresis or diarrhea
• SSRIs Do not normally produce CNS stimulation or mood elevation in normal individuals.
 SSRIs
Drug interactions
• Fluvoxamine has the highest rate of drug interactions, since it inhibits
several hepatic enzymes such as CYP450 1A2, 2C19, 2C9, 2D6, and 3A4
• Fluoxetine inhibits CYP 2C9, 2D6, and 3A4
• Paroxetine is a potent inhibitor of CYP 2D6
• Citalopram and escitalopram have the least drug interactions, since they
inhibit 2D6 enzymes to a lesser extent
• Inhibition of CYP2D6 and CYP3A4 results in elevated plasma levels of TCAs,
haloperidol, clozapine, terfenadine, astemizole, warfarin, β-blockers, some
BZDs and carbamazepine.
 Use in depression
• SSRIs are frequently used as first-line antidepressants because of their ease
of use, tolerability and safety in overdose.
• The choice of a particular SSRI is based upon cost, individual patient
tolerance, and clinician experience because of comparable efficacy
• The starting dose of the SSRIs is usually the same as the therapeutic dose
for most patients, and so titration may not be required.
• Fluoxetine and escitalopram are approved for childhood depression.
• Like other antidepressants, SSRIs take at least 2 weeks for the therapeutic
benefits to appear. The full therapeutic effects of SSRIs may delay for three
to eight (or more) weeks after treatment has started. 
 Other therapeutic uses
• Depression
• Obsessive compulsive disorder (OCD)
• Panic disorder
• Generalized anxiety disorder (GAD)
• Posttraumatic stress disorder (PTSD)
• Social anxiety disorder
• Premenstrual dysphoric disorder
• Bulimia nervosa (only fluoxetine in approved)
SNRIs Inhibit the reuptake of
Venlafaxine both serotonin and
desvenlafaxine,  norepinephrine
Duloxetine
SERT > > NET

and milnacipran
NET > SERT

SNRIs do not have

much affinity for
SNRIs
other receptors
 
 Pharmacokinetics
• Venlafaxine is extensively metabolized in the liver to desvenlafaxine and 4-8% is excreted unchanged
in the urine, whereas, . At least 45% of desvenlafaxine is excreted unchanged in the urine
• Both have similar half-lives of about 8–11 hours. Despite the relatively short half-lives, both drugs are
available in formulations that allow once-daily dosing.
• Venlafaxine and desvenlafaxine have the lowest protein binding of all antidepressants (27–30%).
• Duloxetine is well absorbed and has a half-life of 12–15 hours but is dosed once daily.
• PP binding is 97%.
• It undergoes extensive oxidative metabolism via CYP2D6 and CYP1A2. Hepatic impairment
significantly alters duloxetine levels unlike desvenlafaxine.
• Both milnacipran and levomilnacipran are well absorbed after oral dosing.
• Both have shorter half-lives and lower protein binding than venlafaxine .
• Milnacipran and levomilnacipran are largely excreted unchanged in the urine.
 SNRIs
Adverse effects
• SNRIs have many of the serotonergic adverse effects associated with SSRIs
• Nausea, dizziness and diaphoresis are most common side effect. Nausea can be resolved by taking
these drugs with food.
• SNRIs may also have noradrenergic effects, including increased blood pressure and heart rate, and
CNS activation, such as insomnia, anxiety, and agitation
• Serotonin syndrome when administered with MOIs and other serotonergic drugs
• All the SNRIs are associated with a withdrawal syndrome resembling that seen with SSRI
discontinuation
• Duloxetine is rarely associated with hepatic toxicity in patients with a history of liver damage.
• Withdrawal syndrome is relatively uncommon with milnacipran which also does not cause sexual
dysfunction unlike the other drugs of this class.
• Duloxetine inhibits CYP 2D6 and CYP 3A4.
 Therapeutic uses
• May be effective in depressed patients who do not respond to first
line treatment with SSRIs or develop intolerable side effects
• Some response may appear in 1st two weeks of therapy but full
response may delay for 8-14 weeks.
• These drugs should be taken with food to reduce incidence of
nausea-the most common side effect.
• These drugs may also be effective against chronic painful symptoms:
backache and muscle aches against which SSRIs are ineffective
• Neuropathic pains, such as diabetic peripheral neuropathy
TCAs
TCAs:
Tertiary amine Basic nucleus of TCAs
(clomipramine,
imipramine, These drugs also block
Amitryptyline, histaminergic (H1), α1-adrenergic,
doxepin) and muscarinic receptors.
Blockade of these receptors
SERT >> NET results in several adverse effects

Secondry amine
( desipramine and TCAs were introduced as drug
therapy of depression since 1950s
nortriptyline)
NET > SERT
 Pharmacokinetics
• The TCAs absorb well and have long half-lives.
• Most are dosed once daily at night (due to their sedating
effects).
• Extensively metabolism by CYP2D6. Only 5% dose is excreted
unchanged in the urine.
• Concurrent administration of drugs such as fluoxetine and
genetic polymorphism for CYP2D6 alter plasma levels of TCA.
 TCAs
Adverse effects
• Anticholinergic side effects are the most common: dry mouth, constipation, urinary retention, blurred vision,
and confusion (30 amines > 20 amines)
• Orthostatic hypotension: potent α-blocking property (imipramine is most likely and nortriptyline is least likely to
cause this effect)
• Weight gain, sedation: H 1 antagonism
• Sexual dysfunctions: particularly with highly serotonergic TCAs such as clomipramine
• Diaphoresis
• Cardiotoxicity
• Decrease seizure threshold
• Tremor
• QT prolongation: in overdose
• The TCAs have a prominent discontinuation syndrome (cholinergic rebound)
• TCAs may exacerbate unstable angina, benign prostrate hyperplasia, epilepsy and preexisting arrhythmias.
 Therapeutic uses
• Moderate to severe depression (as second or third line agents)
• Some patients with Phobic and panic anxiety disorders also
respond to TCAs
• Bed wetting in 6 year or older children (imipramine)
• Chronic pain syndrome (eg neuropathic pain)
• Migraine headache
• Insomnia (Doxepin)
 Use in depression
• Clinicians often avoid using tricyclic antidepressants because of their adverse side
effects
• The choice of cyclic antidepressant is often based upon side-effect profiles
because these medications vary in their degree of side effects. Nortriptyline and
desipramine tend to be the best tolerated.
• Therapy should be started with a low dose in order to avoid side effects, which is
slowly increased.
• Response or remission may not occur until four or more weeks have passed after a
therapeutic dose has been achieved
• TCAs have narrow therapeutic index, thus suicidal patients should be given only
limited quantity of these drug with close monitoring.
 Tetracyclc and unicyclic antidepressant
• A number of antidepressants do not fit
neatly into the other classes.
• Unicyclic: Bupropion
• Tetracyclic: mirtazapine, amoxapine,
vilazodone, and maprotiline
• Multicyclic: vilazodone
• Primary use of tetracyclic compound is
MDD.

Vilazodone
 Pharmacokinetics
• Tetra and uni-cyclic compounds are well absorbed orally.
• All the agents undergo extensive first pass metabolism and
have high plasma protein binding
 Tetracyclic and unicyclic antidepressant
Mechanism of Action
• Bupropion: It is norepinephrine-dopamine reuptake inhibitor (NDRI) increases NE and DA but has no effect on
serotonin transmission.
- increases pre-synaptic release of NE and DA
• Mirtazapine: increases release of NE (α2-adrenergic antagonist) and 5-HT, acts as 5HT 2A and 5HT3 blocker. It also
blocks H1 receptors
• Amoxapine and maprotiline: actions resemble those of TCAs such as desipramine.
- Both are potent NET inhibitors and less potent SERT inhibitors.
- In addition, both possess anticholinergic properties.
- Unlike the TCAs or other antidepressants, amoxapine is a moderate inhibitor of the postsynaptic D2
receptor, therefore, posses some antipsychotic properties.
• Vilazodone: A potent serotonin reuptake inhibitor and a partial agonist of the 5-HT1A receptor.

• Antidepressant effect of atypical antidepressant is same as SSRIs and TCA.

 Adverse effects
Bupropion:
• Bupropion is occasionally associated with agitation, insomnia, and anorexia
• It also lowers seizure threshold
• But not have the potential for weight gain
Mirtazapine:
• the most common side effects are dry mouth, marked sedation, appetite increased and weight gain
(>10% individuals), rare side effect is agranulocytosis.
• Bupropion and Mirtazapine are among few antidepressant that cause NO sexual dysfunctions
Amoxapine
• sometimes associated with a parkinsonian syndrome due to its D2-blocking action.
Maprotiline
• has a moderately high affinity for NET and may cause TCA-like adverse effects and, rarely, seizures.
Vilazodone
• may have somewhat higher rates of gastrointestinal upset, including diarrhea and nausea, than the
SSRIs.
 Therapeutic uses
• Atypical antidepressants are frequently used as alternate in
patients with major depression who have inadequate responses
or intolerable side effects during first-line treatment SSRIs.
• Atypical antidepressants are also often first-line treatment if the
drug has a desirable characteristic (eg, sexual side effects and
weight gain occur less often with bupropion than SSRIs).
• Bupropion also helps in tobacco and cocaine withdrawing by
controlling craving symptoms.
 5 HT2
antagonists
(Serotonin
modulators)
5 HT post synaptic
5 HT2A Antagonists receptors
- 5HT 1A, 1B/D
• Trazodone has week inhibitory effect - 5HT 2A, 2C
on SERT and is a H1 receptor and α- - 5HT 3
receptor blocker - 5HT 4
• Nafazodone weakly inhibits SERT and
NET and is H1 receptor blocker
• Vortioxetine: an antagonist of the
5-HT3, 5-HT7, and 5-HT1D
receptors, a partial agonist of the
5-HT1B receptor, and an agonist
of the 5HT1A receptor. It also
inhibits SERT.
 Pharmacokinetics

• Trazodone and nafazodone are rapidly absorbed and extensively metabolized by

liver.
• Both trazodone and nafazodone produce active metabolites that have potent
antagonistic effect on 5-HT2A receptors , but metabolic products of vortioxetine are
inactive.
• Trazodone and nafazodone bind with plasma protein and have short half life so
needed to be administered in multiple doses.
• However, when used as hypnotic, trazodone is given once at night in lower dose
than that required for depression
• The frequency of administration of vortioxetine due to its long half life is once daily.
 Adverse effects
Trazodone:
• Common adverse effects include somnolence, dry mouth, dizziness, fatigue, constipation, vision blurred, orthostatic hypotension, and headache.
• Sexual dysfunctions are uncommon.
• Rare but serious side effects include priapism and cardiac arrhythmias.
Nefazodone:
• Nefazodone can cause hepatotoxicity and is contraindicated in patients with elevated serum transaminases, active liver disease, or liver injury due
to previous nefazodone treatment.
• Other adverse effects of nefazodone include nausea, somnolence, dry mouth, dizziness, constipation, weakness, and blurred vision.
Vortioxetine:
Similar to SSRIs, the most common adverse effects of vortioxetine are serotonergic and include:
• Dose-dependent gastrointestinal effects, particularly nausea and sexual dysfunction. Higher doses of vortioxetine tend to increase the rate of GI
and sexual side effects.
• The teratogenic risks of vortioxetine are not known but like most other antidepressants, it is considered a category C agent.

• All of the above drugs can cause serotonin syndrome

 Use in depression
• Trazodone and nafazodone were among the most commonly prescribed
antidepressants until these drugs were supplanted by the SSRIs in the late 1980s.
• The most common use of trazodone in current practice is as an unlabeled hypnotic,
since it is highly sedating and not associated with tolerance or dependence.
• Low doses of trazodone (50–200 mg) have been used widely, both alone and
concurrently with SSRIs or SNRIs, to treat insomnia.
• Nefazodone is not commonly prescribed due to associated hepatotoxicity.
• Vortioxetine, a newer agent, has demonstrated efficacy in major depression in a
number of controlled clinical studies.
• In addition, vortioxetine is approved in Europe and the USA to treat cognitive
dysfunction associated with depression.
 MAOIs
Non-selective and irreversible- MAOIs
Phenelzine and tranylcypromine,
Selegiline at high dose

Selective (MAO-A) and reversible - Moclobemide

MAO inactivates norepinephrine, dopamine, serotonin.

MAOIs inactivate MAO, permitting neurotransmitter molecules to
accumulate within the presynaptic neuron and leak into the
synaptic cleft and cause activation of NE and serotonin receptors.
 MAOIs
Adverse effects
• Adverse effects have put MAOIs in the second or third line therapy despite
superior efficacy
• The most common adverse effects leading to their discontinuation are orthostatic
hypotension and weight gain
• They can also cause sexual dysfunctions and sleep disturbances
• MAOIs have been associated with a sudden discontinuation syndrome manifested
in a delirium-like presentation with psychosis, excitement, and confusion
• Selegiline and tranylcypromine have an amphetamine like stimulant effect- that
may cause agitation and insomnia.
 MAOIs
Interactions
• MAO-A inhibitors interfere with breakdown of tyramine
• High tyramine levels cause hypertensive crisis (the “cheese
effect”)
• Can be controlled with restricted diet
• Interaction with sympathomimetics leads to hypertensive crisis
• Can cause serotonin syndrome with serotonergic drugs (SSRIs)
(muscle rigidity, fever, seizures)
 Use in depression
• MAOIs are employed in treatment of "atypical" depression (eg,
depression with hyperphagia, hypersomnia, leaden paralysis, and
rejection sensitivity)
• These are frequently effective in treatment-resistant depressed
patients.
• Considered to be last-line agents in the treatment because of their
risk for drug-drug and drug-food interaction
• Like SSRIs and TCAs, the antidepressant action is delayed several
weeks.
 The FDA warning
• An FDA warning applied to all antidepressants is the risk of
increased suicidality in patients under the age 25 who were
prescribed antidepressant in clinical trials
• The warning suggests that use of antidepressants is associated
with suicidal ideation and gestures, but not completed
suicides, in up to 4% of patients
 Clinical uses of antidepressants
Depression
• At present, SSRIs are the most commonly prescribed first-line agents in the treatment of both MDD and
anxiety disorders due to their ease of use, tolerability, and safety in overdose.
• Other agents, including the SNRIs, bupropion and mirtazapine are also reasonable first-line agents for the
treatment of MDD. 
• Titration of dose is usually not required
• Since it takes 1-2 months to achieve maximum therapeutic benefits with antidepressant drugs, therapy
may continue for 8-12 weeks to ascertain effectiveness of a given antidepressant.
• About 30–40% of patients successfully achieve remission within a single trial of 8–12 weeks.
• If an inadequate response is obtained, therapy is often switched to another agent or augmented by
addition of another drug. For example, bupropion, an atypical antipsychotic, or mirtazapine might be
added to an SSRI or SNRI to augment antidepressant benefit if monotherapy is unsuccessful.
• Seventy to eighty percent of patients are able to achieve remission with sequenced augmentation or
switching strategies.
 Clinical uses of antidepressants
• Once an adequate response is achieved, continuation therapy is recommended for a minimum of 6–12
months to reduce the substantial risk of relapse.
• After first episode, MDD may recur in approximately 85% of the patients.
• As a result of multiple recurrences, MDD may progress into more serious, chronic, and treatment-resistant
episodes
• Therefore, long term maintenance treatment is recommended for the patients who have had two or more
serious MDD episodes in the previous 5 years or three or more serious episodes in a lifetime.
• Bupropion,and mirtazapine, and nefazodone are the antidepressants with the least association with
sexual side effects and are often prescribed for this reason.
• The TCAs and MAOIs are now relegated to second- or third-line treatments for MDD. Both the TCAs and
the MAOIs are potentially lethal in overdose, require titration to achieve a therapeutic dose, have
serious drug interactions, and have many troublesome adverse effects. As a consequence, their use in the
treatment of MDD or anxiety is now reserved for patients who have been unresponsive to other agents.
 Clinical uses of antidepressant
Anxiety disorders
• The most common application of antidepressants after depression is anxiety.
• The antidepressants do not carry the risk of tolerance or dependence, as seen with
benzodiazepines, so these are preferred for long term management of generalized anxiety and
panic disorders.
• Clomipramine and several of the SSRIs are approved for the treatment of OCD, and they are
usually combined with Behavior therapy for additional benefits.
• Several SSRIs and venlafaxine are approved for the treatment of social anxiety.
• SSRIs are considered first-line treatment for PTSD and can benefit a number of symptoms including
anxious thoughts and hypervigilance. These are given with psychotherapeutic interventions.
 Clinical uses of antidepressant
Pain disorders (chronic and neuropathic pain)
• Serotonin and norepinephrine reuptake inhibitors (TCAs and SNRIs)
are useful in pain disorders
• duloxetine has been approved for the treatment of chronic joint and
muscle pain.
• Milnacipran is approved for the treatment of fibromyalgia in the USA
• Other SNRIs, eg, desvenlafaxine, are being investigated for a variety
of pain conditions from postherpetic neuralgia to chronic back pain.
 Clinical uses of antidepressant
Premenstrual Dysphoric Disorder:
• During late luteal phase of almost every cycle, approximately 5% of women in the
child-bearing years will have prominent mood and physical symptoms (anxiety,
depressed mood, irritability, insomnia, fatigue, and a variety of other physical
symptoms).
• These symptoms are more severe than those typically seen in premenstrual
syndrome (PMS) and can be quite disruptive to vocational and interpersonal
activities.
• The SSRIs (fluoxetine and sertraline) are approved for this indication.
• Treating for 2 weeks out of the month in the luteal phase may be as effective as
continuous treatment.
 Clinical uses of antidepressant
Smoking cessation
• Bupropion was approved in 1997 as a treatment for smoking
Cessation to reduced urge to smoke.
Eating disorder (Bulimia nervosa)
• Fluoxetine has been approved for treatment of bulimia nervosa
Obesity
• Bupropion has shown some benefits in reducing weight among
the non-depressed obese patients compared to placebo.
 Clinical uses of antidepressant
Other uses
• Enuresis in children – TCAs
• Stress urinary incontinence: SNRI (duloxetine)
• Vasomotor symptoms on perimenopause (Desvenlafaxine)
• Premature ejaculation (SSRIs)
 Choice of antidepressants
• In general, antidepressant medications have been shown to be equally efficacious for MDD
• Therefore, medication choice should be based on adverse effects, drug interactions, safety,
and patient preferences
• Elderly patients are particularly sensitive to anticholinergic effects of TCAs.
• the CYP3A4-inhibiting effects of the SSRI fluvoxamine may make this a problematic choice in
some older patients because fluvoxamine may interact with many other medications that an
older patient may require
• bupropion and other antidepressants are known to lower the seizure threshold in epilepsy
patients.
• Patients with narrow-angle glaucoma may have an exacerbation with noradrenergic
antidepressants
• When considering patient characteristics and safety, SSRIs are safe to use in most patient
groups, including those with preexisting cardiac disease, asthma, dementia, and
hypertension
 Choice of antidepressants
• In addition, SSRIs are also inexpensive
• Other agents, including the SNRIs, bupropion, and mirtazapine, are also reasonable first-line
agents for the treatment of MDD.
• Bupropion, mirtazapine, and nefazodone are the antidepressants with the least association
with sexual side effects and are often prescribed for this reason.
• The TCAs and MAOIs are now relegated to second- or third-line treatments for MDD.
• Both the TCAs and the MAOIs are potentially lethal in overdose, require titration to achieve
a therapeutic dose, have serious drug interactions, and have many troublesome adverse
effects. As a consequence, their use in the treatment of MDD or anxiety is now reserved for
patients who have been unresponsive to other agents.
• Clearly, there are patients whose depression responds only to MAOIs or TCAs. Thus, TCAs
and MAOIs are probably underused in treatment-resistant depressed patients.
Thank you