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Mood Disorder. Major Depressive Disordered I. Jawza F. Al-Sabhan, Msc. College of Pharmacy Clinical Pharmacy Department. Introduction.

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Major depressive disordered i

Mood Disorder

Major Depressive Disordered I

Jawza F. Al-Sabhan, Msc.

College of Pharmacy

Clinical Pharmacy Department


  • Everyone experiences variations in mood, blues that come and go, disappointments, the normal grief that accompanies the loss of someone you love. But a severe or prolonged depression that interferes with the ability to function or feel pleasure is not a mere

    case of the blues. It is an illness.

  • Depression affects many people of all ages.

  • It is the 8th leading cause of death for males, and 19th leading cause of death for females.


  • Lifetime incidence of depression is 13-20%.

  • Life time incidence of depression in KSA 17%.

  • Life time prevalence 5-12%(US,Europe)

  • Most common age is late 20s.

Pathophysiology hypotheses
Pathophysiology hypotheses

Biogenic amine

1. Central nervous system (CNS) deficiency in dopamine, norepinephrine, and/or serotonin

2. Based on knowledge that antidepressants increase monoamine neurotransmission


An underlying deficiency of serotonin accompanied by decreased noradrenergic transmission

Pathophysiology hypotheses1
Pathophysiology hypotheses

Neuroendocrine finding

  • Pituitary and adrenal glands are enlarged in depressed patients, and hypothalamic function may be abnormal.

  • Serotonin exerts a strong influence on HPA axis.

  • Approximately 45% to 60% of patients with major depression have a neuroendocrine abnormality, including hypersecretion of cortisol

Noradrenergic tracts

Noradrenaline, a key neurotransmitter involved in the control of mood and emotional behavior, is believed to inhibit or stimulate a variety of emotional responses such as anxiety, aggression, stress, and sleep

Serotonergic tracts

Serotonin is involved in the regulation of pain, pleasure, anxiety, panic, appetite , and sleep behavior (the sleep-wake cycle).

Risk factors
Risk factors

1. Family history of depression

a. 1st degree relative of patients with depression are 1.5 to 3 times more likely to develop depression

b. Twin studies

• Monozygotic twins have a 65% concordance rate for depression

• Dizygotic twins have a 14% concordance rate for depression

2. Female gender

3. Previous depressive episode

4. Chronic medical illness

5. Substance abuse

Diagnostic criteria dsm iv for mdd
Diagnostic Criteria (DSM-IV)for MDD

  • At least 5 symptoms present for 2 weeks most of day nearly every day

  • Represents change from previous functioning

    a. Depressed mood*

    b. Loss of interest or pleasure*

    c. Appetite or weight change

    d. Sleep disturbance

    e. Psychomotor agitation/retardation

    f. Fatigue/loss of energy

    g. Feelings of worthlessness/guilt

    h. Decreased concentration/indecisiveness

    i. Recurrent thoughts of death/suicidal ideation/suicide attempt

    3. Symptoms cause social or occupational impairment

    4. Symptoms are not due to substance abuse or medical condition

    5. Symptoms are not due to gereavement

Depression sub classification

A-Melancholia (endogenous)

Weight loss

Early morning awakening

Extreme listlessness

Intense guilt

Inability to cheer up even for a moment

B- Psychotic (or delusional)

Mood congruent

Poverty, physical illness, moral transgressions

Occur in 10–25%

C-Atypical depression (exogenous)

Increased appetite

Weight gain

Excessive sleep

Leaden sensation in the arms and legs

Mood reactive

D-Postpartum Depression

Onset of depression within 4 weeks

occurs in 10% to 26%

Depression Sub-classification

Specific features of diagnosis
Specific features of diagnosis

1) Mild

a) Minimum requirement to make diagnosis

b) Minor functional impairment

2) Moderate

  • Greater degree of functional impairment

    3) Severe

    a) Marked interference with social and/or occupational functioning

    b) Suicidal ideation

Target symptoms
Target symptoms

  • D — depressed mood

  • S — sleep

  • I — interest

  • G — guilt

  • E — energy

  • C — concentration

  • A — appetite

  • P — psychomotor

  • S — suicide

Laboratory studies
Laboratory studies

  • There are no diagnostic lab tests for depression, although the following should be obtained to rule out other medical illnesses which mimic depression

    a. Complete blood count (CBC; i.e., anemia)

    b. Thyroid function tests (TFTs; i.e., hypothyroidism)

    c. Rapid plasma reagin (RPR; i.e., syphilis)

    d. Urine drug screen (i.e., substance abuse)


  • 70% of patients are responsive to antidepressant therapy

    2. Relapse

    a. Following 1st episode, 50% experience another episode

    b. Following 2nd episode70% experience another episode

    c. Following 3nd episode 90% experience another episode


  • Patients who lack capacity to cooperate with treatment

  • Patients at risk for suicide or other violent behavior

  • Patients who lack psychosocial supports

  • Patients who have other psychiatric or general medical problems.

Rating scales
Rating scales

  • General purpose

    a. Brief Psychiatric Rating Scale (BPRS), investigator-rated

    b. Hopkins Symptom Checklist (SCL-90), patient-rated

  • Disease-specific rating scales (depression)

    a. Investigator-rated

    1) Hamilton Rating Scale for Depression (Ham-D, HRSD)

    2) Montgomery-Asburg Depression Rating Scale (MADRS)

    b. Patient-rated

    1) Beck Depression Inventory (BDI)

    2) Zung Self Rating Scale

Choices of treatment


a. Less severe

b. Less chronic

c. No psychotic

d. Past positive response

e. Medical contraindication to medications


a. More severe

b. Chronic

c. Recurrent

d. Psychotic

e. Melancholic

f. Past positive response

g. Family history

h. Failure to respond to psychotherapy

Choices of Treatment

Choices of treatment1

Medication and psychotherapy

a. More severe

b. Chronic

c. Partial response to either therapy alone

d. Personality disorder

Electroconvulsive therapy

a. Psychotic

b. Severe or extremely severe

c. Past positive response

d. Failure of several medications or combined treatment trials

e. Need for rapid response

f. Medical contraindications to medications

Choices of Treatment

Antidepressant therapy
Antidepressant therapy

  • Initiation of therapy

    • Initiate therapy with divided doses to minimize adverse drug reactions

    • Consider age of patient and adjust accordingly

    • Target dose should be achieved as quickly as tolerated

    • Improvement in 3–4 weeks of therapy

    • Maximal response in 8 weeks of therapy

Acute treatment

Duration usually 6–12 weeks

Response (symptom remission)

a) Definition

i) Complete (> 50% reduction)

ii) Partial (> 20% but < 50%)

iii) No response (< 20%)

b) Rate of response

i) First week

• Decreased anxiety

• Improvement in sleep

• Improvement in appetite

ii) 1–3 weeks

• ↑ Activity, sex drive, self-care, memory

• Thinking and movements normalize

• Sleeping and eating patterns normalize

iii) 2–4 weeks

• Relief of depressed mood

• Less hopeless/helpless

• Thoughts of suicide subside

Acute treatment

Continuation treatment
Continuation treatment

  • To prevent relapse

  • Continue antidepressant 6–9 months after 1st episode at same dose

  • Continue with the same treatment and the same dose in acute phase.

Maintenance treatment
Maintenance treatment

  • 1 year duration

  • Use full therapeutic doses

  • Goal is to prevent new episode (recurrence)

  • Potential candidates

    a) Three episodes of MDD or

    b) Two episodes of MDD and:

    i) Family history of borderline personality disorder/recurrent MDD in 1st degree relative

    ii) Recurrence within 1 year after medicine discontinued

    iii) Onset before age 20 or after age 60

    iv) Severe, sudden or life threatening depression

Factors to be consider on selection of an antidepressant
Factors to be consider on Selection of an antidepressant

  • Neurotransmitter profile family history

  • Side effect profile potential drug interactions

  • Patient age

  • cost

  • ease of administration (compliance)

  • Safety profile

Antidepressant medication

  • Antidepressants can be classified in several ways, including by chemical structure and the presumed mechanism of antidepressant activity.

  • All antidepressants are potentially effective in the treatment of depression, they show similar efficacy when used in adequate dosages.


  • TCA = Tricyclic Antidepressants

  • MAOI = Mono- Amines Oxides Inhibitor

  • SSRI = Selective Serotonin Reuptake Inhibitor

  • SNRI = Serotonin Reuptake Inhibitor

Antidepressant medication2

Tricyclics “TCAs”

  • Amitriptyline 50 –300 mg/day

  • Clomipramine 50 –250 mg/day

  • Doxepin 25 –300 mg/day

  • Trimipramine 50 –300 mg/day

  • Imipramine 50 –300 mg/day

  • Desipramine 50 –300 mg/day

  • Nortriptyline 25 –150 mg/day

  • Protriptyline 10 – 60 mg/day


Secondary amines

Mechanism Of Tricyclic Antidepressants TCA

Antidepressant medication3


  • Block the reuptake of both norepinephrine(NE) , serotonin (5HT),muscarinic, alpha1 adrenergic, and histaminic receptors.

  • The extent of these effects vary with each agent resulting in differing side effect profiles.

  • TCA have effects on cardiac action potentials typical of class IA antiarrhythmics

Tricyclic antidepressants
Tricyclic Antidepressants Antidepressant Drugs*

Managements of Anticholinergic side effects.

  • Impaired visual accommodation may be counteracted through the use of pilocarpine eye drops.

  • Urinary hesitation may be treated by prescribing bethanechol, 200 mg/day

  • Dry mouth may be counteracted by advising the patient to use sugarless gum or candy or by prescribing an oral rinse of 1% pilocarpine used three or four times daily.

  • Constipation is best dealt with through adequate hydration and the use of bulk laxatives.

Tricyclic antidepressants1
Tricyclic Antidepressants Antidepressant Drugs*


  • TCAs also have affinity for histaminergic receptors and produce varying degrees of sedation.

  • In general, tertiary amines cause greater sedation, whereas secondary amines cause less.

  • Patients with major depressive disorder with insomnia may benefit from sedation when their medication is given as a single dose before bedtime.

Tricyclic antidepressants2
Tricyclic Antidepressants Antidepressant Drugs*

Weight gain.

  • TCAs have the capacity to induce weight gain possibly through their histaminergic properties.

  • The degree of weight gain appears to vary by agent (e.g., greater weight gain with amitriptyline and less with desipramine), be dose dependent, and be reversible with cessation of tricyclic antidepressant therapy.

Tricyclic antidepressants3
Tricyclic Antidepressants Antidepressant Drugs*

Neurological effects.

  • TCAs can induce mild myoclonus, this may be a sign of toxicity.

  • Amoxapine, a TCA with antipsychotic properties, can also cause extrapyramidal side effects and tardive dyskinesia.

  • In overdoses, tricyclic antidepressants can precipitate seizures especially (Maprotiline).

Antidepressant medication4

Monoamine oxidase irreversible, non

selective inhibitors “MAO Is”

  • Phenelzine 15 –90 mg/day

  • Tranylcypromine 10 – 60 mg/day

  • Inhibit the enzymatic breakdown of 5HT and NE.

  • They are usually reserved for atypical or resistant depression due to their toxicityprofile.

Antidepressant medication5

Reversible monoamine oxidase

inhibitors ”RIMA”

  • Moclobemide

  • This unique mechanism results in a good tolerability profile and unlike traditional MAOIs, there is no need to restrict dietary tyramine.

Monoamine oxidase inhibitors
Monoamine oxidase inhibitors Antidepressant Drugs*

Hypertensive crises.

  • A hypertensive crisis can occur when a patient taking an MAOI ingests large amounts of tyramine or other pressor amines in foods or medications.

  • This reaction is characterized by the acute onset of severe headache, nausea, neck stiffness, palpitations, profuse perspiration, and confusion, possibly leading to stroke and death.

Monoamine oxidase inhibitors1
Monoamine oxidase inhibitors Antidepressant Drugs*

Hypertensive crises.

  • Dietary restrictions include avoiding such foods as aged cheeses or meats, fermented products, yeast extracts

  • The list of medications that must be avoided includes all sympathomimetic and stimulant drugs as well as over-the-counter decongestants and cold remedies.

Monoamine oxidase inhibitors2
Monoamine Oxidase Inhibitors Antidepressant Drugs*

Cardiovascular effects.

  • Orthostatic hypotension is commonly seen during MAOI treatment.

  • Possible treatments for this side effect include the addition of salt to increase intravascular volume or use of the steroid fludrocortisone.

  • MAOI use can also be associated with the development of peripheral edema, which may be helped by the use of support stockings.

Major depressive disordered ii

Major Depressive Disordered Antidepressant Drugs*II

Jawza F. Al-Sabhan, Msc.

College of Pharmacy

Clinical Pharmacy Department

Antidepressant medication6

Comparative efficacy
COMPARATIVE EFFICACY Antidepressant Drugs*

  • SSRIs have a flat dose-response curve. There is seldom any advantage in dosing higher than the usually effective minimum dose.

  • TCAs, and other atypical antidepressants appear to have an ascending dose-response curve, thus higher doses are usually associated with increased efficacy.

Comparative safety
COMPARATIVE SAFETY Antidepressant Drugs*

  • Most current literature considers the SSRIs to be better tolerated than TCAs, especially when used at the minimally effective dose.

  • One meta-analysis has disputed this, arguing that dropout rates (~32%) are not significantly different for either group.

Antidepressant medication7

Selective serotonin reuptake inhibitors “SSRIs”

  • Fluoxetine 20–40mg/day

  • Sertraline 50 –200 mg/day

  • Paroxetine 20–40 mg/day

  • Fluvoxamine 50 –300 mg/day

  • Citalopram 20 – 40 mg/day

  • Escitalopram 10-20 mg/day

Mechanism of SSRI Antidepressant Drugs*

Antidepressant medication8

Selective Serotonin Reuptake Inhibitors

  • Block the reuptake of 5HT and increase synaptic 5HT transmission.

  • They have little or no effect on other neurotransmitters, results in fewer anticholinergic (ACH) and sedative effects.

Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors Antidepressant Drugs*


  • SSRIs cause nausea, vomiting, and diarrhea to a greater extent than tricyclic antidepressant medications.

  • These adverse events are generally dose dependent and tend to dissipate over the first few weeks of treatment.

Selective serotonin reuptake inhibitors1
Selective serotonin reuptake inhibitors Antidepressant Drugs*


  • In some patients, SSRIs may precipitate or exacerbate restlessness, agitation, and sleep disturbances.

  • These side effects often attenuate with time.

  • Anxiety may be minimized by introducing the agent at a low dose; insomnia may be effectively treated by the addition of trazodone, up to 100 mg at bedtime.

Selective serotonin reuptake inhibitors2
Selective serotonin reuptake inhibitors Antidepressant Drugs*

Sexual side effects.

  • loss of erectile or ejaculatory function in men and loss of libido and anorgasmia in both sexes may be complications SSRIs.

  • Lowering the dose, discontinuing the antidepressant, or substituting another antidepressant such as bupropion

  • Specific pharmacologic treatments that can be added for arousal or erectile dysfunction include sildenafil, yohimbine.

Selective serotonin reuptake inhibitors3
Selective serotonin reuptake inhibitors Antidepressant Drugs*

Effects on weight.

  • Fluoxetine has been shown to cause an initial reduction in weight but this tends be gained back subsequently.

  • The literature differs as to whether patients taking SSRIs beyond the acute phase do or do not experience weight gain as a medication side effect.

Selective serotonin reuptake inhibitors4

Serotonin syndrome. Antidepressant Drugs*

SSRI used associated with the rare development of a syndrome due to an excess of serotonergic activity.

Features of serotonin syndrome include:

(abdominal pain, diarrhea, flushing, sweating, hyperthermia, lethargy, mental status changes, tremor and myoclonus, rhabdomyolysis, renal failure, cardiovascular shock, and possibly death.)

it is usually associated with the simultaneous use of multiple serotonergic agents such as SSRIs together with MAOIs.

When patients are being switched from an SSRI with a short half-life to an MAOI, a waiting period of at least 2 weeks is needed between the discontinuation of one medication and the initiation of the other.

When switching from fluoxetine to an MAOI, a waiting period of at least 5 weeks is needed before the MAOI is started.

Selective serotonin reuptake inhibitors

Atypical AD Antidepressant Drugs*

Antidepressant medication9

Atypical Antidepressants

Norepinephrine-serotonin modulator

  • Mirtazapine 15 – 45 mg/day

    Serotonin-norepinephrine reuptake inhibitors 

  • Venlafaxine 75 –375 mg/day

    Dopamine-norepinephrine reuptake inhibitors

  • Bupropion 150 – 450 mg/day

MIRTAZAPINE Antidepressant Drugs*

  • The drug mainly affects serotonin (5-HT) receptors of the 5-HT2 and 5-HT-3 subtypes, possessing low affinity for 5-HT1A, 5-HT1B, and 5-HT1C receptors; as a 5-HT2 antagonist.

  • mirtazapine has strong alpha-2 receptor blocking actions, but unlike mianserin it has no significant effect on the synaptic reuptake of catecholamines.

Mirtazipine side effects

  • The most common side effects from mirtazapine include sedation, dry mouth, and weight gain.

  • Mirtazapine has also been shown to increase serum cholesterol levels in some patients.

  • Although agranulocytosis has been observed to occur in patients taking mirtazapine.

VENLAFAXINE Antidepressant Drugs*

  • Venlafaxine is selectively inhibits neuronal uptake of serotonin, norepinephrine.

  • The initial recommended dosage of regular-release venlafaxine is 75 milligrams (mg)/day; the dose may be titrated at 4-day intervals to a maximum dose of 375 mg/day.

  • Major Side Effect: Hypertension

BUPROPION Antidepressant Drugs*

  • Bupropion is a very weak inhibitor of norepinephrine uptake and a weak inhibitor of dopamine uptake.

  • Side effect including headaches, tremors, and seizures.

Pharmacologic effects of antidepressants
Pharmacologic Effects Of Antidepressants Antidepressant Drugs*

Reduce depression

Psychomotor activation

Antiparkinsonian effects

Reduce depression

Reduce suicidal behavior

Antipsychotic effects


Ejaculatory dysfunction




Weight gain








Blurred vision

Dry mouth


Sinus tachycardia

Urinary retention

Cognitive dysfunction

Reduce depression

Antianxiety effects

GI disturbances

Sexual dysfunction

ACh block


5HT reuptake










Reduce depression

Antianxiety effects



Erectile/ejaculatory dysfunction

Postural hypotension


Reflex tachycardia

Memory dysfunction

Electroconvulsive therapy ect
Electroconvulsive Therapy ECT Antidepressant Drugs*


Electroconvulsive therapy involves applying a brief electrical pulse to the scalp while the patient is under anesthesia. This pulse excites the brain cells causing them to fire in unison and produces a seizure.

Cont ect
Cont. Antidepressant Drugs*ECT



Nursing staff

Cont ect1
Cont. Antidepressant Drugs*ECT

Bilateral Placement

Right Unilateral Placement

Comparative pharmacokinetics
Comparative Pharmacokinetics Antidepressant Drugs*

Drug interactions
Drug Interactions Antidepressant Drugs*

  • Newer antidepressants and CYP P450 inhibitory enzymes

Drug interactions1
Drug Interactions Antidepressant Drugs*

  • TCAs

    a) TCA + anticoagulant → ↑ anticoagulant effect

    b) Enzyme inhibitors → ↑ TCA effect

    c) Enzyme inducer → ↓ TCA effect

    d) TCA + centrally-acting antihypertensive → ↑ BP

    e) TCA + sympathomimetic → ↑ BP plus arrhythmias

    f) TCA +MAOI → hypertensive crisis

Drug interactions2
Drug Interactions Antidepressant Drugs*

  • MAOIs

    a) MAOI + stimulant → hypertensive crisis

    b) MAOI + antidiabetics → hypoglycemia

    c) MAOI + insulin → hypoglycemia

    d) MAOI + levodopa → hypertensive crisis

Drug interactions3
Drug Interactions Antidepressant Drugs*

  • SSRI

    a) SSRI + TCA → ↑ TCA effect

    b) SSRI + carbamazepine → ↑ carbamazapene

    d) SSRI + antipsychotic → ↑ antipsychotic effect

    e) SSRI + warfarin → ↑ bleeding time

    f) SSRI + MAOI → serotonergic syndrome

Special populations Antidepressant Drugs*

Special populations
Special Populations Antidepressant Drugs*


1) Treatment

a) Mild depression—psychotherapy

b) Severe depression with decreased oral intake, suicidality, or psychosis—pharmacotherapy or electroconvulsive therapy (ECT)

2) Antidepressants of choice

a) Well-studied during pregnancy (tricyclic antidepressants [TCAs], fluoxetine)

b) Short-acting (sertraline, paroxetine)

Special populations1
Special populations Antidepressant Drugs*

  • Lactation

    1) Antidepressants of choice

    a) Well-studied (?)

    b) Improved pharmacokinetic profiles

    c) Limited metabolites

    d) Greater receptor selectivity

    2) Specific agents

    a) Sertraline, paroxetine

    b) Nortriptyline, desipramine

Special populations2
Special populations Antidepressant Drugs*

  • Elderly

  • Treatment considerations

    a) Pharmacokinetic and pharmacodynamic changes

    b) Coexisting medical conditions (e.g., cardiovascular disease)

    c) Anticholinergic side effects

    d) Depression-related cognitive dysfunction (pseudo-dementia)

  • Agents of choice

    a) Short-acting selective serotonin reuptake inhibitors (SSRIs)

    b) Bupropion

Concurrent medical disorders Antidepressant Drugs*

Concurrent medical disorders
Concurrent medical disorders Antidepressant Drugs*

  • Asthma

    a) Avoid monoamine oxidase inhibitors (MAOIs) which interfere with sympathomimetic bronchodilators

  • Cardiac disease

    a) Ventricular arrhythmia, subclinical sinus node dysfunction, conduction defects

    b) Avoid TCAs

    c) Use bupropion, SSRIs or ECT

    d) MAOIs do not affect cardiac conduction, rhythm, or contraction but may induce orthostasis

Concurrent medical disorders1
Concurrent medical disorders Antidepressant Drugs*

  • Dementia

    a) Avoid TCAs or antidepressants with anticholinergic properties

  • Epilepsy

    a) Avoid bupropion, maprotiline, amoxapine, TCAs

  • Glaucoma (narrow-angle)

    a) Avoid TCAs

Concurrent medical disorders2
Concurrent Medical Disorders Antidepressant Drugs*

  • Hypertension

    a) TCAs may antagonize the therapeutic actions of guanethidine, clonidine, or methyldopa

    c) Concurrent antihypertensive treatment, especially with diuretics, increases likelihood that TCAs, MAOIs, or trazodone will induce orthostasis

    d) β-blockers, esp. propranolol may cause depression

  • Parkinson’s disease

    a) Avoid amoxapine (dopamine-receptor blocker)

Patient Education Antidepressant Drugs*

Patient education
Patient Education Antidepressant Drugs*

  • Treat the patient with the same empathy, respect, and concern that you would treat a patient with a medical illness

  • Do not be afraid to discuss the symptoms of depression

  • Be sensitive to the patient’s fear of being stigmatized

  • Emphasize the common occurrence of depression as well as the many successful treatment options

  • Compare depression to a common and accepted medical illness (e.g., diabetes or hypertension)

  • Compare the need for medication compliance with antidepressants to the need for compliance with other maintenance medications (e.g., insulin or antihypertensive agents).

Thank god for his mercy, Antidepressant Drugs*

who carry a hope for us

with every sunrise!