DEPRESSION

2011 data from the World Health

Organization (WHO) showed that the
Philippines has the highest incidence of
depression in Southeast Asia with 93
suicides for every 100,000 Filipinos
 DEPRESSION
• Depression afflicts approximately 5% of
the population, 1-2% with bipolar
disorder.
• Suicide from depression is 25-30% of
depressed population.
• Depression 2-3 X higher in women.
• 70% of patients have good responses to
medications
• Myths
– 54% believe depression is a weakness not
an illness
– 62% believe depression is not a health
problem
– >50% believe depression is “normal” and
will not seek treatment
Genetic factors influence risk of
illness and sensitivity to
environmental factors.
A family history of depression is a risk factor for
developing depression.
CLINICAL SYMPTOMS OF DEPRESSION
• loss of pleasure (anhedonia) • difficulty concentrating
• loss of energy • indecisiveness
• social withdrawal • sad thoughts/thoughts of
psychomotor retardation or suicide
agitation
• hopelessness
• insomnia
• loss of appetite • helplessness
• decreased hygiene • guilt/shame
• crying spells
 BIOLOGY OF DEPRESSION
• the “amine hypothesis” based on
pharmacological studies stated that
depression resulted from a lack of biogenic
amines
• current theory favors the notion of a
deregulation of both NE and 5-HT leading to
alterations in NE and 5-HT receptors
• ANTIDEPRESSANTS RE-REGULATE RECEPTOR
SENSITIVITY
 SEROTONIN-A KEY PLAYER
• Serotonin has widespread distribution and
density of innervation in CNS (mood, memory,
pleasure, aggression, hypothalamic control)
 ANTIDEPRESSANTS
Classifications
1. Tricyclic Antidepressants (TCAs)
2. Selective Serotonin Reuptake Inhibitors
(SSRIs)
3. Atypical (heterocyclic second- and third-
generation) Antidepressants;
4. Monoamine Oxidase Inhibitors (MAOIs).
 CLINICAL PHARMACOLOGY OF
ANTIDEPRESSANTS
• Indications: depression, panic and phobias, OCD, enuresis,
anorexia nervosa, bulimia

• Drug Choice: past response, tolerance to side effects, drug-

drug interactions

• Treatment: 1-6 months; recent report suggests changing if

no improvement by 4 weeks

• Note: All antidepressants now carry a “black box” warning

that they may lead to suicidal thoughts/behavior
 POSSIBLE MECHANISMS
• All antidepressants downregulate a-adrenergic
receptors and presynaptic 5-HT-1a/b
• Antidepressants decrease number of amine
transporters
• Long-term treatment with SSRI causes 6-fold
increase in 5-HT release
 Mechanisms of Action
TCAs and
Atypical Antidepressant Drugs
• TCAs and atypical antidepressant drugs
potentiate the actions of norepinephrine,
serotonin, or both by blocking their uptake by
transporters into prejunctional nerve endings,
the major route for their physiologic
inactivation.
 MAOIs
• MAOIs rapidly, nonselectively, and essentially
irreversibly inhibit the activity of enzymes MAO-A
and MAO-B. Inhibition of MAO-A, which
preferentially degrades norepinephrine and
serotonin, is responsible for the therapeutic
efficacy of MAOIs as antidepressants
• MAOIs act as ‘‘suicide’’ enzyme inhibitors, with
inhibition continuing for up to 2–3 weeks after
their elimination from the body.
 Therapeutic Efficacy
• Therapeutic efficacy of these drugs occurs
after several weeks of antidepressant
administration
• Closely associated with adaptive changes over
the same time period
 Therapeutic Use
Major Depressive Disorder
• Antidepressant drugs elevate mood, increase
physical activity and mental alertness,
increase appetite and sexual drive, improve
sleep patterns, and reduce preoccupation
with morbid thoughts.
• These drugs are effective in 70% of patients.
SSRIs are preferred over TCAs
because of their more limited
toxicity.
MAOIs are used rarely.
 Other Uses
• Bipolar affective disorder
• Anxiety disorders (generalized anxiety disorder (GAD)
and panic disorder (PD); Obsessive–compulsive
disorder (OCD)– treated with clomipramine; social
phobia (SP); situational anxiety disorder (SAD); and
post-traumatic stress disorder (PTSD))
• Enuresis (children over age 6, and adults)
• Attention-deficit/hyperactivity disorder (ADHD)
• Chronic pain
• Bulemia
• Premenstrual dysphoric disorder
 TCAs
Pharmacologic Properties

• TCAs are generally highly lipid-soluble and

have relatively long half-lives
• Plasma levels are used primarily to monitor
compliance and toxicity
TCAs Adverse Effects
• Sedation
• Confusion and memory dysfunction
• Mania (occurs in patients with an underlying
bipolar affective disorder— ‘‘switch’’ reaction)
• Agitation and psychosis may worsen in psychotic
patients
• Tremor (occurs in 10% of patients)
• Seizures
• Movement disorders (usually with amoxapine)
TCAs Adverse Effects
• Postural hypotension
• Tachycardia, conduction defects, arrhythmias
(common with overdose particularly with
imipramine; patients with preexisting heart
block or compensated cardiac output are at
risk)
• weight gain that can be extensive
• sexual dysfunction
TCAs Adverse Effects
• may increase suicidal ideation for children,
adolescents, and young adults (‘‘blackbox’’
warning)— particularly with Atomoxetine
TCAs Adverse Effects
• Autonomic nervous system effects reflect the
muscarinic cholinoceptor antagonist activity
(temporary and more common in the elderly)–
dry mouth, blurred vision, difficulty in
urination, and constipation. May precipitate
narrow-angle glaucoma or paralytic ileus or
cause urine retention.
 TCAs

Rebound/Discontinuation Effects
• dizziness, nausea, headache, and fatigue
• may persist for up to 2 months
• tapered withdrawal minimizes effects
TCAs Overdose and Toxicity
• severe anticholinergic and antiadrenergic
signs
• respiratory depression
• Arrhythmias
• Shock
• Seizures
• Coma
• death
SSRIs Adverse Effects
• Headache
• Sexual dysfunction in up to 40% of all patients
(leading cause of non-compliance)
• Gastric irritation
• Weight loss initially followed in some patients
by weight gain
• Apathy
Atypical Antidepressant
Agents
(The pharmacologic properties of
atypical antidepressant agents are
similar to those of TCAs.)
 Adverse Effects
• Trazodone effects:
✓ highly sedating (assoc. with dizziness)
✓ nausea
✓ postural hypotension in the elderly
✓ significant anticholinergic activity
• Mirtazepine causes marked weight gain
• The seizure risk with maprotiline may be 4% at
high therapeutic doses
• Amoxapine
✓ Movement disorders similar
 Adverse Effects
• Venlafaxinen
✓Nausea
✓Dizziness
✓sexual disturbances
✓Anxiety
✓Insomnia
• MAOIs Adverse Effects
• postural hypotension
• Headache
• dry mouth
• sexual dysfunction (phenelzine)
• weight gain
• sleep disturbances
 SEROTONIN SYNDROME
• A potentially fatal interaction when SSRI’s and
MAOI’s are combined
• Symptoms:
• autonomic instability (labile HR/BP)
• hyperthermia
• rigidity and myoclonus
• confusion,delirium
• seizures
• coma
 “WINE-CHEESE EFFECT”
• MAOI’s enhance any indirectly acting
sympathomimetic

• tyramine in certain foods is not metabolized in

presence of MAOI and potentiates catecholamine
release

• ingredients in OTC cold preps can also lead to

markedly enhanced sympathomimetic effects
particularly resulting to hypertensive crisis
DRUG SUMMARY
THANK YOU! ☺