DEPRESSION

• Depression is a affective disorder.

• Affective disorders : mental illnesses characterized
by pathological changes in mood.
• Depression : pathologically depressed mood
 DEFINITIO
N
• DEPRESSION: Common mental disorder that
presents with depressed mood, loss of interest or
pleasure, feelings of guilt or low self- worth,
disturbed sleep or appetite, low energy, and poor
concentration.
 TYPES OF
•
DEPRESSION
Major depressive disorder : recurrence of long
episodes of low moods, or one extended episode that
seems to be ‘never-ending.
- Atypical depression
- Postpartum depression
- Catatonic depression
- Seasonal affective disorder
- Melancholic depression
• Dysthymic depression
- lasts a long time but
involves less severe symptoms.
- lead a normal life, but we may not
be functioning well or feeling
good
• Situational depression
• Psychotic depression
• Endogenous depression
MAJOR DEPRESSIVE DISORDER

 aka unipolar depression

 lifetime prevalence:
up to 21% in women
13% in men
 typical age of onset:
20s, but can occur at any time
 SYMPTOMS OF MDD
• Feelings of sadness, tearfulness, emptiness or hopelessness
• Angry outbursts, irritability or frustration, even over small matters
• Loss of interest or pleasure in most or all normal activities, such as sex,
hobbies or sports
• Sleep disturbances, including insomnia or sleeping too much
• Tiredness and lack of energy, so even small tasks take extra effort
• Reduced appetite and weight loss or increased cravings for food and
weight gain
• Anxiety, agitation or restlessness
• Slowed thinking, speaking or body movements
• Feelings of worthlessness or guilt, fixating on past failures or self-blame
• Trouble thinking, concentrating, making decisions and remembering
things
• Frequent or recurrent thoughts of death, suicidal thoughts, suicide
attempts or suicide
• Unexplained physical problems, such as back pain or headaches
 ATYPICAL DEPRESSION

Described in DSM-IV
Depression that shares many of the typical
symptoms of the major depression or dysthymia
But is characterized by improved mood in response
to positive events.
It also features significant weight gain or an
increased appetite, hypersomnia, a heavy sensation
in the limbs, and interpersonal rejection sensitivity
that results in significant social or occupational
impairment
 POSTPARTUM DEPRESSION
• Also called Postnatal depression
• Associated with childbirth
• Can affect both sexes
• Symptoms may include: extreme sadness, low
energy, anxiety, crying episodes, irritability, and
changes in sleeping or eating patterns
• Onset is typically between one week and one
month following childbirth
• PPD can also negatively affect the newborn child
 CATATONIC DEPRESSION
 Catatonic depression affects the individual’s motor skills
 Can be caused by other underlying mental health disorders,
such as schizophrenia, mood disorders, and post-traumatic
stress disorder
 People with catatonia remain still and do not respond to any
events/things around them
 There are three types of catatonia: akinetic, excited and
malignant catatonia
 Akinetic catatonia is the most commonly observed in
people with catatonic depression
 Malignant catatonia can be dangerous, causing severe
health effects
 SIGNS AND SYMPTOMS
Automatic obedience – The patient automatically obeys all instructions
given by the doctor
Ambitendency – The patient alternates between cooperating with the
doctor’s instructions and resisting them
Aversion – The patient turns away when he or she is being spoken to
Echopraxia – The patient imitates the activities of the person speaking with
him or her.
Excitement – The patient engages in excessive and purposeless action that
is not driven by outside stimuli
Negativism – The person is always having negative thoughts and feels sad
every day
Stupor – This is one of the common signs of catatonia. It is characterized by
a lack of mobility and speech
Posturing – The person remains in the same posture for a long period of
time
Mutism – The person is verbally unresponsive and refuses to speak
Staring – The individual’s eye is fixed on a particular space and open for
long periods of time.
 SEASONAL DEPRESSION
 More than just "the winter blues"
 Seasonal depression is often called seasonal affective
disorder (SAD)
 Occurs at the same time each year
 Linked to reduced exposure to sunlight during the shorter
autumn and winter days (production of Melatonin, Serotonin
and Circadian rhythm)
Symptoms:
• A persistent low mood
• A loss of pleasure or interest in normal everyday activities
• Irritability
• Feelings of despair, guilt and worthlessness
• Feeling lethargic (lacking in energy) and sleepy during the day
• Sleeping for longer than normal and finding it hard to wake up
• Craving carbohydrates and gaining weight
 MELANCHOLIC DEPRESSION
 Melancholic depression, or depression with
melancholic features
 Is a DSM-IV and DSM-5 subtype of clinical
depression
Signs and Symptoms
• Requiring at least one of the following symptoms:
• Anhedonia
• Lack of mood reactivity
• And at least three of the following:
• Depression that is subjectively different from grief or loss
• Severe weight loss or loss of appetite
• Psychomotor agitation or retardation
• Early morning awakening
• Guilt that is excessive
• Worse mood in the morning
 Double Depression

 Dysthymic disorder with episodes of

major depression
 Prognosis more negative
 EPIDEMIOLOG
•
Y
Globally more than 350 million people of all ages
suffer from depression. (WHO)
• For the age group 15-44 major depression is the
leading cause of disability in the U.S.
• Women are nearly twice as likely to suffer from a
major depressive disorder than men are.
• With age the symptoms of depression become even
more severe.
• About thirty percent of people with depressive
illnesses attempt suicide.
 ETIOLOG
• Genetic causeY
• Environmental factors
• Biochemical factors : Biochemical theory of
depression postulates a deficiency of
neurotransmitters in certain areas of the brain
(noradrenaline, serotonin, and dopamine).
• Dopaminergic activity : reduced in case of
depression, over activity in mania.
• Endocrine factors
- hypothyroidism, cushing’s
syndrome
• Abuse of Drugs or Alcohol
• Hormone Level Changes
• Physical illness and side effects of
medications

DRUGS
• Analgesics
• Antidepressants
• Antihypertensives
• Anticonvulsants
• Benzodiazipine withdrawal
• Antipsychotics
 PHYSICAL
ILLNESS
• Viral illness
• Carcinoma
• Neurological disorders
• Thyroid disease
• Multiple sclerosis
• Pernicious anaemia
• Diabetes
• Systemic lupus erythematosus
• Addison’s disease
 PATHOPHYSIOLOGY
• The Biogenic Amine Hypothesis
• The Receptor Sensitivity Hypothesis
• The Serotonin-only Hypothesis
• The Permissive Hypothesis
• The Electrolyte Membrane
Hypothesis
• The Neuroendocrine Hypothesis
• The Biogenic Amine Hypothesis
- caused by a deficiency of
monoamines, particularly noradrenaline and
serotonin.
-cannot explain the delay in time of onset of
clinical relief of depression of up to 6-8 weeks.
• The Receptor Sensitivity Hypothesis
-depression is the result of a pathological
alteration (supersensitivity and up-regulation) in
receptor sites.
- TCAs or MAOIs causes desensitization (the
uncoupling of receptor sites) and possibly down-
regulation (a decrease in the number of receptor sites).
• The Serotonin-only Hypothesis
- emphasizes the role of serotonin in
depression and downplays noradrenaline.
- But the serotonin-only theory has
shortcomings:
- it does not explain why
there is a delay in onset of clinical relief
- it does not explain the role of NA
in depression.
• The Permissive Hypothesis
-the control of emotional behavior results from
a balance between noradrenaline and serotonin.
-If serotonin and noradrenaline falls to
abnormally low levels, the patient becomes
depressed.
-If the level of serotonin falls and the level
of noradrenaline becomes abnormally high, the
patient becomes manic.
• The Electrolyte Membrane Hypothesis
- hypocalcemia may be associated
with mania.
- hypercalcemia is associated with
depression.

• The Neuroendocrine Hypothesis

- pathological mood states are explained
or contributed to by altered endocrine
function.
CLINICAL MANIFESTATIONS
• DEPRESSIONS
o Thinking is pessimistic and in some cases
suicidal.
o In severe cases psychotic symptoms such
as hallucinations or delusions may be
present.
o Insomnia or hypersomnia, libido, weight loss, loss of
appetite.
o Intellectual or cognitive symptoms include a
decreased ability to concentrate, slowed thinking, & a
poor memory for recent events.
 DIAGNOSI
S
• ICD 10 Diagnostic criteria for a
depressive episode (WHO)
USUAL SYMPTOMS
• Depressed mood.
• Loss of interest and enjoyment.
• Reduced energy leading to
increased fatiguability and
diminished activity.
 COMMON
SYMPTOMS
• Reduced concentration and attention.
• Reduced self esteem and self confidence.
• Ideas of guilt and unworthiness.
• Bleak and pessimistic views of future .
• Ideas or acts of self harm or suicide.
• Disturbed sleep.
• Diminished appetite.
 MILD DEPRESSIVE EPISODE

• For at least 2 weeks, at least two of the usual

symptoms of a depressive episode plus at least
two common symptoms.
MODERATE DEPRESSIVE EPISODE
• For at least 2 weeks, at least two or three of the
usual symptoms of a depressive episode
plus at least three of the common symtoms.
 SEVERE DEPRESSIVE EPISODE

• For at least2 weeks all three of the usual

symptoms of a depressive episode plus at
least 4 of the common symptoms some of
which should be of severe intensity.
 INVESTIGATIONS
• RATING SCALES
o Beck depression inventory
o Hamilton depression rating scale
• DEXAMETHASONE SUPPRESSION TEST
 TREATMENT
ANTIDEPRESSANTS
1. MAO inhibitors:
• Irreversible: Isocarboxazid, Iproniazid, Phenelzine and
Tranylcypromine.
• Reversible: Moclobemide and Clorgyline.
2. Tricyclic antidepressants (TCAs)
• NA and 5 HT reuptake inhibitors : Imipramine,
Amitryptiline, Doxepin, Dothiepin and
Clomipramine.
• NA reuptake inhibitors : Desimipramine,
Nortryptyline, Amoxapine.
3. Selective Serotonin reuptake inhibitors:
• Fluoxetine, Fluvoxamine, Sertraline and
Citalopram
4. Atypical antidepressants:
• Trazodone, Mianserin, Mirtazapine,
Venlafaxine, Duloxetine, Bupropion and
Tianeptine
 MAO Inhibitors
• Drugs act by increasing the local availability of NA
or 5 HT.
• MAO is a Mitochondrial Enzyme involved
in Oxidative deamination of these amines.
o MAO-A: Peripheral nerve endings, Intestine
and Placenta (5-HT and NA).
o MAO-B: Brain and in Platelets (Dopamine).
o Selective MAO-A inhibitors (RIMA) have
antidepressant property
(eg:Moclobemide).
• Side effects : postural hypotension,
weight gain, atropine like effects and
CNS stimulation.
• Severe hypertensive response to tyramine
containing foods-cheese reaction
• Drug interaction : Ephedrine, Reserpine.
 TCAs
• NA, 5 HT and Dopamine are present in Nerve
endings
• Normally, there are reuptake mechanism and
termination of action.
• TCAs inhibit reuptake and make more monoamines
available for action.
• In most TCA, other receptors (incl. those outside the
CNS) are also affected: blockade of H1-receptor,
Alpha-receptors, M-receptors.
 SSRIs
• First line drug in depression.
• Relatively safe and better patient acceptability.
• Some patients not responding to TCAs may
respond with SSRIs.
• SSRIs inhibit the reuptake mechanism and
make more 5 HT available for action.
 Relative advantages:  Drawbacks:
– No sedation, so no – Nausea is common
cognitive or – Interfere with
psychomotor function ejaculation
interference – Insomnia, dyskinesia,
– No anicholinergic
headache and
effects diarrhoea
– No alpha-blocking – Impairment of platelet
action, so no postural function – epistaxis
hypotension and
suits for elderly
– No seizure induction
– No arrhythmia
SSRIs – Pharmacokinetic comparison
 Atypical antidepressants
1. Trazodone:
• Weak 5-HT uptake block, α – block, 5-HT2 antagonist
• No arrhythmia
• No seizure
• ADRs: Postural Hypotension
2. Venlafaxine:
• SNRI (Serotonin and NA uptake inhibitor)
• Fast in action
• No cholinergic, adrenergic and histaminic interference
• Raising of BP
3. Mianserin
• Not inhibiting either NA or 5 HT uptake, but blocks
presynaptic alpha-2 receptors- increase release of
NA in brain.
• ADR : Blood dyscrasias, liver dysfunction.
4. Bupropion
• Inhibitor of DA and NA uptake (NDRI)
• Non-sedative but excitant property
• Used in depression and cessation of smoking
• Seizure may precipitated
 Serotonin Syndrom
• A group of symptoms that may occur with the use of
certain serotonergic medications or drugs
• The degree of symptoms can range from mild to severe,
including a potentiality of death
• Symptoms in mild cases include high blood pressure and
a fast heart rate; usually without a fever
• Symptoms in moderate cases include: fever,
agitation, increased reflexes, tremor, sweating, dilated
pupils, and diarrhea
• In severe cases body temperature can increase to greater
than 41.1 °C. Complications may include seizures
and extensive muscle breakdown, kidney failure and
unconsciousness
 Causes of Serotonin Syndrom
• Selective serotonin reuptake inhibitors
• Serotonin and norepinephrine reuptake inhibitors Bupropion an
antidepressant and tobacco-addiction medication
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• Anti-migraine medications, such as carbamazepine, valproic acid and
triptans
• Pain medications, such as opioid pain medications including codeine,
fentanyl, oxycodone
• Lithium a mood stabilizer
• Illicit drugs, including LSD, ecstasy, cocaine and amphetamines
• Herbal supplements, including St. John's wort, ginseng and nutmeg
• Over-the-counter cough and cold medications containing
dextromethorphan
• Anti-nausea medications such as granisetron, metoclopramide and etc.
• Linezolid an antibiotic
• Ritonavir an anti-retroviral medication used to treat HIV
 Treatment of Serotonin Syndrom
Depending on your symptoms, you may receive the following
treatments:

 Muscle relaxants. Benzodiazepines, they can help control

agitation, seizures and muscle stiffness.
 Serotonin-production blocking agents
 Oxygen and intravenous (IV) fluids. Breathing oxygen
through a mask helps maintain normal oxygen levels in your
blood, and IV fluids are used to treat dehydration and fever.
 Drugs that control heart rate and blood pressure. 
 A breathing tube and machine and medication to paralyze
your muscles. You may need this treatment if you have a
high fever.
 NON – PHARMACOLOGIC
THERAPY
• LIFESTYLE CHANGES
o Stress reduction
o Social support
o Sleep
• PSYCHOTHERAPY
o Cognitive behavioral therapy
o Interpersonal therapy
o Psychodynamic therapy
 Comparing Treatments
Studies compare CBT and IPT to antidepressant
meds and other control conditions
results
CBT, IPT, and meds are equally effective
CBT, IPT, and meds are more effective than
placebo conditions
brief psychodynamic treatments
other control conditions
50-70% of people benefit from treatment to a
significant extent, compared to 30% in placebo or
control conditions
 Combined Treatments

 Meds work more quickly

 Psychosocial treatments:
 Increase long-range social
functioning
 Prevent relapse
• ELECTROCONVULSIVE THERAPY
– ECT
o Safe & effective disorder for all subtypes
of major depressive disorder.
o ADR : Cognitive dysfunction,
cardiovascular dysfunction,
prolonged apnoea etc.
 CONCLUSIO
• N
Affective disorders remain one of the most
commonly occurring mental illnesses in adults.
• It is often undiagnosed and untreated.
• Both pharmacological and nonpharmacological
interventions acts as cornerstone in the treatment
of affective
disorders.
• Pharmacist plays an important role in
accomplishing these treatment goals.