Major Depressive Disorder

Dr. Ali Altajli

Head of unit 2 at KCMH

Head of ECT team
 DIAGNOSTIC CRITERIA
A. Five (or more) of the following symptoms have been present
for TWO WEEKS. At least one of the symptoms is either (1) or
(2):
1. Depressed mood
(Note: in children and adolescents, can be irritable mood).
2. Anhedonia
Markedly diminished interest or pleasure .
 3. Weight loss or gain (5% in a month), or decrease or
increase in appetite.
4. Insomnia or hypersomnia.
5. Psychomotor agitation or retardation.
6. Fatigue or loss of energy.
7. Feelings of worthlessness (low self- esteem) or excessive or
inappropriate guilt.
 8. Diminished ability to think or concentrate, or
indecisiveness (pseudodementia).
9. Recurrent thoughts of death, recurrent suicidal ideation
without a specific plan, or a suicide attempt or a specific
plan for committing suicide.
 UNIPOLAR VERSUS BIPOLAR DEPRESSION
Unipolar depression is known now as Major Depressive Disorder.
All mood episodes are depressive in nature. Treated with
antidepressants mainly and we may add antipsychotics.
Bipolar depression is a part of either bipolar I (depressive
alternating with manic episodes) or bipolar II (depressive
alternating with hypomanic episodes). Not treated with
antidepressants but treated mainly with mood stabilizers.
 GRIEF MDE
1. Feelings of emptiness and loss. 1. Persistent depressed mood and anhedonia.
2. Decreased with time. 2. Persistent.
3. Pain may be accompanied by positive 3. Pervasive unhappiness and
emotions or humor. misery.
4. Thought content: memories of the 4. Self-critical or pessimistic
deceased. ruminations.
5. Preserved self-esteem. 5. Lost self-esteem.
6. Joining the deceased. 6. Ending one’s own life.
 How to write diagnosis
Major depressive disorder, single or recurrent episode, severity/psychotic/remission
specifiers. Followed by any of these specifiers:
1. With anxious mood.
2. With mixed features.
3. With melancholic features.
4. With atypical features.
5. With mood-congruent psychotic features.
6. With mood-incongruent psychotic features.
7. With catatonia.
8. With peripartum onset.
9. With seasonal pattern.
 WITH ANXIOUS MOOD
TWO of the followings:
1. Feeling tense.
2. Restless.
3.Difficulty concentrating because of worry.
4. Fear that something awful will happen.
5. Feeling that one might loss control.
 WITH MIXED FEATURES
Significant risk factors for the development of bipolar I or II disorder.
Need 3 from the following
1. Elevated mood.
2. Inflated self-esteem or grandiosity.
3. More talkative.
4. Flight of ideas.
5. Excessive involvement in activities that have a high potential for
painful consequences.
6. Decreased need for sleep.
 WITH MELANCHOLIC FEATURES
1. LOSS OF PLEASURE.
2. LACK OF REACTIVITY TO USUALLY P[EASURABLE STIMULI.
Need 1 of the above in addition to 3 or more of the following .
- Empty mood.
- Worse in the morning.
- Early-morning awakening.
- Marked psychomotor agitation or retardation.
- Significant anorexia or weight loss.
- Excessive guilt.
 WITH ATYPICAL FEATURES

MOOD REACTIVITY IN ADDITION TO 2 OR MORE OF THE

following.

1. SIGNIFICANT WEIGHT GAIN OR INCREASE IN APPETITE.

2. HYPERSOMNIA.
3. LEADEN PARALYSIS.
4. A LONG-STANDING PATTERN OF INTERPERSONAL REJECTION
SENSITIVITY.
 Depressive disorders prevalence
• 5-10% in the community
• 10-20% in the primary care & 30 % of all visits for GP
• 20-30% for the medically I'll inpatient
• 70% of psychiatric patients receive treatment only in primary care.
Patient with depression may have comorbid psychiatric conditions:
1. Anxiety disorders 30%
2. Sub. Use
3. Others
 Why Depression Care is Important
•Prevalence rates are approximately 2.3–3.2% in men and
4.5–9.3% in women .
•Prevalence in primary care 10-13% .
•Lifetime risk for developing an episode of 7–12% for men and
20 –25% for women
•World-wide is the 4th most disabling medical condition, climbing
to 2nd in 2020.
•Primary care provides at least 50 –90 % of care for depressed
outpatient
 The Burden of Depression

Personal and Economic cost of Depression

Depressed adults have twice the annual health care costs as non-
depressed.
Under-treated condition.
•only 46-57% of the 12 million cases in the United States are
receiving treatment for major depression.
•only 18-25% is adequately treated.
 The Burden of Depression

ØWHO 2017 reported that depression is the leading cause of

disability as it has a major effect on quality of life for patients
and families
ØThe economic burden of depression is due to (management,
admission ,treatment, impairment and absentism)
Depressive disorders are Unnoticed in primary care

• In primary care settings , depression disorders are unnoticed &

undetected & if treated it is either with inadequate doses or
inadequate time or both.
 Why is depression so difficult to diagnose?
According to cross sectional studies 50-70% of patients with
depression in primary care remain undetected, Due to
o About two thirds of depressed patients present mainly with
somatic symptoms , directing the physician away from diagnosing
depression and results in a missed diagnosis.
o Comorbidity of depression with other medical condition
o Social stigma
o Lack of proper psychiatric training for physicians
o During consultation the discussion should move away from somatic
symptoms to emotional health by asking patients open questions.
 Detection & Recognition
The detection of depression can be improved by training in
mental health and careful screening for patients at high risk in
both primary care and general hospital settings (for example,
those with :
o Headache, migraines
o Sexual dysfunction
o Appetite changes
o Menstrual-related symptoms
 Detection & Recognition

o Chronic pain
o Chronic medical conditions (eg, diabetes, Parkinson's disease,
alcoholism)
o Digestive problems (eg, diarrhea, constipation)
o Sleep disturbances fatigue, appetite or weight change
o Unexplained physical symptoms
 Detection & Recognition
Simple screening for depression is by asking two questions on mood
and interest .

1. Have you been bothered by little interest or pleasure in doing

things?
2. Have you been feeling down, depressed, or hopeless in the last
month?

However, the diagnosis must be obtained through determining

whether the criteria for depression are met .
SCREENING
 PHQ-9
Self-report, in person, by phone, on-line, interactive voice-
response
•Multiple languages.
•Multiple patient populations (elderly, those with medical
problems, etc)
•Over 700 articles published on use of the tool in various settings.
 Scales
• Beck Depression Inventory Self-Reporting Questionnaire 21
Question
• The 20-item Zung Depression Self-Rating Scale .
• The Geriatric Depression Scale (GDS) is a self-report measure
designed to minimize the impact of somatic symptoms
associated with aging and illness. (the 15-item version, using a
cutoff of five)
• Hamilton. Scale
• Montgomery Asperg scale
Antidepressant Medication
 Antidepressant Medication
o Only half of the patients will respond to antidepressant treatment
and only one-third of patients experience a full remission of
symptoms.
o Response to antidepressants may take 3 to 4 weeks even 6 weeks
o If no response after 2 trials of full therapeutic dose and full
duration , pt will be considered therapy resistant depression.
o All new generation antidepressants have same efficacy
o Withdrawal symptoms are present but short lived and mostly very
mild .
o antidepressants are not addictive.
 Antidepressant Medication
• The identification of genetic biomarkers that predict
antidepressant treatment response can improve current
clinical practice.
• Recent studies on antidepressant treatment response have
focused on new candidate genes that may predict better
treatment response for patients.
 Evaluating the efficacy of treatment for
depression.
• Non-response—25% or less decrease in symptom severity
compared with baseline
• Partial response—25-50% decrease in symptom severity
compared with baseline
• Response—50% or greater decrease in severity of symptoms
compared with baseline
• Remission—absence of symptoms defined by absolute scale
(for example, score of ≤7 on Hamilton rating scale for
depression) Adapted from World Federation of Societies of Biological
Psychiatry guideline
 Antidepressant Medication

• Antidepressants - TCAs, MAOIs, SSRIs & SNRIs

• The discovery of antidepressants could be described as a ‘lucky

accident’.
• During the 1950s, while carrying out trials on a new
medication for tuberculosis (TB), researchers noticed that the
medication also had a mood improving effect.
 1-Two classes of first generation antidepressants:
TCAs & MAOIs
• Tricyclic Antidepressants (TCAs), of which the most widely used
type was:
Ø Amitriptyline (tryptizol).
Ø Imipramine (Tofranil).
Ø Clomipramine (Anafranil).

• Monoamine Oxidase Inhibitors (MAOIs),of which the two most

widely used types were:
Ø Moclobemide (aurorix).
Ø Phenelzine.
 Effects vs side effects
• Both TCAs and MAOIs proved to be effective in treating
depression, but they did cause a wide range of side effects,
which were often unpleasant. These included:

• Constipation, urinary retention.

• Blurred vision ,acute angle glaucoma.
• shaking or trembling, and sweating.
• difficulty sleeping.
 2-Second generation antidepressants
SSRIs
• The second generation of antidepressants, which are collectively known as
Selective Serotonin Reuptake Inhibitors (SSRIs), were introduced at the
beginning of the 1980s. Commonly used were:
· Fluoxetine (Prozac- salipax).
· Citalopram, escitalopram (cipralex).
· Paroxetine (seroxate).
· Sertraline (Zoloft) .
fluvoxamine (faverin).

• SSRIs quickly became widely used instead of TCAs and MAOIs as they
were considered to cause far less troublesome side effects.
 Common side effects
• nausea (feeling sick) .
• low sex drive .
• dizziness .
• feeling agitated or shaky .
• insomnia (not sleeping well) or feeling very sleepy .

• Weight gain
 3-Serotonin noradrenaline reuptake inhibitor
SNRIs

• The third generation of antidepressants, which are collectively

known as Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs),
were introduced during the 1990s. Examples of SNRIs include:
• Venlafaxine(effexor), Desvenlafaxine(pristic) , Trazodone
• Duloxetine (Cymbalta) , Milnacipran(ixel).
• SNRIs were the result of an attempt to create an antidepressant
that was more clinically effective than SSRIs. However, the evidence
that SNRIs are more effective at treating everyone with depression
is uncertain.
 Advantages & Side effects
Advantages:
• less weight gain.
• May help with somatic symptoms.
Side effects:
• nausea (feeling sick).
• low sex drive .
• Hypertension .
• Used carefully with cardiovascular patients.
• Irritability.
 4-Norepinephrine Dopamine reuptake inhibitor
• Wellbutrin (bupropion) classified as a norepinephrine &
dopamine reuptake inhibitor, is used to treat depression as an
add on medication, also used for smoking cessation .
Advantages :
• No weight gain and no sexual side effects
• Can be added for resistant depression to SSRI.
 5-Multimodal Antidepressants
• Brintellix (Vortioxetine) 10mg - 20mg
• Increase release of several different neurotransmitters
{serotonin –dopamine –norepinephrine - acetylcholine and
glutamate}also block reuptake of serotonine.
• Mode of action are complicated but unique.
Advantages :
o Improves cognition in depression
o Can be used for old age depression
 Side effects
• GIT symptoms.
• Possible hyponatreamia.

BUT:
• Rare sexual side effects
• No weight gain
 6-Noradrenergic and specific serotonergic agonist
NASSA
• Remeron (mirtazapine) is a noradrenergic and specific
serotonergic agonist .
• used for major depression.
Advantages :
• Rare sexual side effects.
• Improve sleep.
• Can be used as augmentation for other antidepressants.
Side effects :
• Weight gain.
• Hypersomnia.
 7-Melatonergic agonists
Agomelatine (valdoxan 25mg-50mg )
• Works on melatonine M1 & M2 receptors.
• 5 HT2c antagonist and increase dopamine secretion,
It is said to help in Anhedonia .
Advantages :
• Rare sexual side effects .
Side Effects :
• Increase in liver enzymes. monitoring is mandatory.
 Brain
Stimulation
Therapy
 Overview
• Electroconvulsive Therapy (ECT)
• Vagus Nerve Stimulation (VNS)
• Repetitive Transmagnetic Stimulation (r.TMS)
• Magnetic Seizure Therapy (MST)
• Deep Brain Stimulation (DBS)
Electroconvulsive Therapy
 Indications
• Severe treatment resistant depression.
• Bipolar disorders.
• Mania.
• Schizophrenia + other psychosis, Catatonia.
• Hypopituitarism.
• Intractable Seizure Disorder.
• Neuroleptic Malignant Syndrome (NMS).
• Parkinson disease.
 Contraindications
• No Absolute CI – Mostly relative.
• Space Occupying Lesions (leading to I.C.P).
• Recent M.I.
• Recent I.C.H.
• Bleeding or Unstable Vascular aneurysm.
• Retinal Detachment.
• Phaeochromocytoma.
• Anesthetic risk rated as ASA 4,5.
 Side Effects
• Cognitive dysfunction. review pt meds, ECT Technique, tx
frequency.
• Arrythmias and Blood pressure changes.
• Prolonged Apnea.
• Prolonged Seizure.
• Switch to mania or hypomania.
• H/A, N and muscle aches.
 How ECT Works
• To date no conclusive answers.
• However, plenty of ideas proposed.
• Over 50 theories to date.
 Mostly Accepted Theories
• Anticonvulsants.
• Anti-delirium/Sleep deprivation.
• Neurogenesis (Hippocampal proliferation).
• Neurotransmitters (NA, Serotonin, GABA, Glu).
• Intracellular changes – BDNF.
• Neuroendocrine changes.
• Melatonin.
• Neuropeptides.
-electrodes placement technique
Canadian Guideline for Use of ECT
ECT Video
Vagus Nerve
Stimulation
 VNS
• Device implanted under the skin that sends electrical pulses
through the left vagus nerve.
Indication:
• Epilepsy, mood disorders.
• The pulses appeared to alter the level of certain
neurotransmitters (serotonin, NA, GABA, Glu).
 FDA Regulation
• Approved for treatment of resistant depression (2005).
FDA CRITERIA:
• Pt: 18 years of age or over.
• Illness lasted 2 years or more.
• Severe or recurrent.
• Not eased after trying at least 4 other treatments.
• (Note: Recent study, 32% of depressed patients responded to
VNS and 14% had full remission after treatment for 2 years).
 How does it work?
• Device implanted in the upper left side of the chest. Connected
to an electrical lead wire which in turn attached to the left
vagus nerve.
• Typically 30 seconds of electrical pulses are sent every 5
minutes to the left vagus nerve and then delivers those signals
to the brain.
• Patients do not feel pain when the device operates.
• The device can be deactivated at anytime by placing a magnet
e.g. S/Es, engaging in sternous activity.
• Notes:
1. response may take several months
2. Not all patients respond to VNS
3. VNS is usually given with other traditional therapies.
 VNS Side Effects
• Infection.
• Device may come loose or malfunction.
• Voice changes or hoarseness.
• Cough or soar throat.
• Neck pain.
• Discomfort or tingling around the implant.
• Breathing problems (exercise).
• Difficulty swallowing.
 Repetitive
Transmagnetic
Stimulation
 r.TMS
• Uses a magnet instead of electricity (ECT, VNS).
• 1st developed in 1985.

• Indicated: depression, psychosis, anxiety, etc.

• 2008 approved by EDA for treatment of major depression.

Area of interest:
• Left dorsolateral prefrontal cortex (DLPFC).
 How Does It Work?
• Typical r.TMS sessions last 30-60 minutes.
• No need for anesthesia.
• Electromagnetic coil is held against the forehead near the area of
the brain involved in mood regulation.
• Short electromagnetic pulses pass through the skull and cause
small electrical currents that stimulate nerve cells in the targeted
brain region.
• The magnetic field is about the same strength as that of an MRI
scan.
• Lacks evidence for solo use.
 r.TMS Side Effects
• Discomfort at the site of application (magnet).
• Muscle twitches of the scalp, jaw during procedure.
• Mild H/A, brief light headedness.
• Seizure.
Magnetic Seizure Therapy
 MST
• Like r.TMS has magnetic pulses.
• But unlike r.TMS induces seizure like ECT.
• Patient needs to be anasthetized as in ECT, however causes less
cognitive side effects.
 Side Effects
• Anesthesia risks.
However:
• fewer memory side effects.
• Shorter seizures.
• Shorter recovery time than ECT.
Deep Brain Stimulation
 DBS
• 1st Parkinson disease.
• Pair of electrodes, implanted in the brain and controlled by a
generator implanted in the chest.
• Indicated: depression, OCD.
 How It Works
• Needs surgery. Patient awake during the procedure to provide
the surgeon with feedback.
• Head is anesthetized so patient feels no pain.
• In depression, the subgenial cingulate cortex targeted (usually
overactive in depression).
• In OCD the ventral capsule/ventral striatum targeted.
 DBS Side Effects
• Hmg or Stroke.
• Infection.
• Disorientation or confusion.
• Unwanted mood swings.
• Movement disorders.
• Light headedness.
• Trouble sleeping.