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It is one of the most common psychiatric
disorder, characterized by intense feeling of
sadness, hopelessness , and despair and
inability to experience ordinary pressure to
cope with ordinary life events
Complications
When depression is neglected or severe it When depression is neglected or severe it can lead to:can lead to:
-Suicide -Substance abuse -Alcoholism -Heart problems-Work-related problems -Family conflicts-Social isolation
Unipolar depression
is more common and affects old patients who are subjected to certain circumstances associated with
Anxiety. Mood remains at one emotional state or pole."[
Patients are usually inert
Bipolar depression develops early in life and a hereditary factor may
be involved, and patients oscillate between depression and mania
Old classification of depression
Factors affecting depression
Several risk factors appear to work together to cause or precipitate depressive disorders,
the most important of these are: Genetic influences
Environmental Biological factors
Genetic influencesGenetic influences
Some types of depressions like bipolar and Some types of depressions like bipolar and the early onset depression the early onset depression (before the age (before the age
of 25) of 25) are thought to be genetically are thought to be genetically determined disorders. determined disorders. Identical twin Identical twin
studies revealed that if one of them suffers studies revealed that if one of them suffers from depression or manic-depressive from depression or manic-depressive
disorder, the other twin has a disorder, the other twin has a 70 %70 % chance chance of having the illnessof having the illness
EnvironmentalEnvironmental
11 ) )Early childhood trauma or abuseEarly childhood trauma or abuse
22 ) )Loneliness and lack of social supportLoneliness and lack of social support
33 ) )Recent stressful or traumatic lifeRecent stressful or traumatic life
experiencesexperiences
44 ) )Alcohol and drugsAlcohol and drugs
55 ) )Finances and employmentFinances and employment
66 ) )Health problems or chronic painHealth problems or chronic pain
Biological factors
Imbalances of neurotransmitters ; mainly
serotonin (5-HT) and norepinephrine (NE) play a major role in pathogenesis
of depression
5-HT deficiency may cause the sleep problems ,irritability, and anxiety associated with depression
Decreased level of NE, which regulates mood ,alertness, arousal, appetite, reward & drives, may
contribute to the fatigue and depressedmood of the illness
However, dopamine )D) is important for pleasure,sex & psychomotor activity
Theories of DepressionTheories of Depression
The etiology of depression is too complex to be totally explained by a single theory
1 .Neurotrophic hypothesis
2 .The monoamine theory
3 .The dysregulation hypothesis
4 .Neuro-endocrinal hypothesis
Pharmacotherapy
Electroconvulsive therapy )ECT)
Psychotherapy
Therapies for depression
IndicationsIndicationsECT can be life-saving & produce dramatic ECT can be life-saving & produce dramatic relief forrelief for::
--Pregnant patientsPregnant patients
--Patients intending suicidePatients intending suicide
--Intractable maniaIntractable mania
--Some cases of psychotic depressionsSome cases of psychotic depressions
--People who cannot take antidepressants People who cannot take antidepressants due to problems of health or compliancedue to problems of health or compliance
Monoamine nerves: Neurotransmission
Sites of Action for Antidepressants
1 -Monoamine (NE or/ and 5-HT) re-uptake pump inhibitors
2 -Blockade of pre-synaptic 2 receptors
3 -Inhibition of MAO enzyme
Classification of Classification of Antidepressant DrugsAntidepressant Drugs
Tricyclic antidepressantsTricyclic antidepressants
# #TCAs are the oldest class of antidepressant drugsTCAs are the oldest class of antidepressant drugs
# #They have characteristic three-ring nucleusThey have characteristic three-ring nucleus
# #Older agents ‘first generation’ TCAs;Older agents ‘first generation’ TCAs; Imipramine – Amitriptyline Imipramine – Amitriptyline are the prototypical are the prototypical
drugs of the class as mixed NE & 5-HT reuptakedrugs of the class as mixed NE & 5-HT reuptake
inhibitorsinhibitors
# #They can be used for long duration for Rx of They can be used for long duration for Rx of depression without loss of effectivenessdepression without loss of effectiveness
Mechanism of ActionMechanism of Action
TCAs inhibit the neuronal reuptake of TCAs inhibit the neuronal reuptake of NE NE
and 5HTand 5HT into presynaptic nerve terminals into presynaptic nerve terminals
leading to an increased concentration of leading to an increased concentration of
these monoamines in the synaptic cleft in these monoamines in the synaptic cleft in
the brainthe brain
N.B. Like phenothiazines, TCAs block N.B. Like phenothiazines, TCAs block
adrenergic (adrenergic (αα11), histamine (H), histamine (H11)and )and
muscarinic (Mmuscarinic (M11)receptors)receptors
Classification of TCAsClassification of TCAs
Tertiary aminesTertiary amines --Block the reuptake ofBlock the reuptake of
55--HT& NEHT& NE
- -more side effectsmore side effects
11 - -ImipramineImipramine
22 - -AmitriptylineAmitriptyline
Secondary aminesSecondary amines - -More selective to More selective to NENE
--less side effectsless side effects
11 - -DesipramineDesipramine
22 - -NortriptylineNortriptyline
Tetracyclic antidepressentsTetracyclic antidepressentsMaprotiline: has a strong H1 blocking activity = Maprotiline: has a strong H1 blocking activity =
sedative effectsedative effect
TCAs: Secondary vs Tertiary AminesTCAs: Secondary vs Tertiary Amines
Tertiary
Secondary
Pharmacological actionsPharmacological actions
11 - -Elevate moodElevate mood
22 - -Improve mental alertnessImprove mental alertness
33 - -Increase physical activityIncrease physical activity
# #The antidepressant effect may develop after several The antidepressant effect may develop after several
weeks of continued treatment ( 2 - 3 weeks)weeks of continued treatment ( 2 - 3 weeks)
44 - -In non-depressed patients In non-depressed patients They cause They cause
sedation, confusion & motor incoordinationsedation, confusion & motor incoordination
1 -Treatment of major depression& panic disorders
2 -Depressed phase of bipolar depression with mood stabilizer
3 -Obsessive-compulsive disorders4 -Together with antipsychotics in
Rx of depressed psychotic patients5-Treatment of resistant depression that
has failed to respond to standard SSRI therapy
Clinical indications
5 -Imipramine used to control bed-wetting in children
) nocturnal enuresis )
by causing contraction of ’internal sphincter of ’ bladder
6 -Analgesia in neuropathic pain chronic painful states ) They modulate opioid
systems in the CNS)
Clinical indications
Adverse Effects
1 -Anticholinergic effects: dry mouth, blurred vision, constipation & urine retention,
aggravation of glaucoma2 -Antihistaminic effects: Sedation, confusion
Sedation wear off in 1-2 weeks as the anti- depressant effect develops
5 -Metabolic-endocrine: weight gain, sexual disturbances
3 -CV effects: postural hypotension, due to
blockade of α-adrenoceptors and reflex tachycardia
4 -Neurologic: seizures
5- TCAs have narrow therapeutic index.
6 -Depressed patients tend to be suicidal
7 -may be fatal in overdose (arrhythmia)
Selective Serotonin Reuptake Inhibitors
SSelective elective SSerotonin erotonin RReuptake euptake IInhibitors: SSRI’snhibitors: SSRI’s
# #First highly selective 5HT-reuptake First highly selective 5HT-reuptake inhibitorsinhibitors
# #Little or no effect on NE reuptakeLittle or no effect on NE reuptake
# #First choice for most depressionFirst choice for most depression
# #Clinical efficacy for major depression Clinical efficacy for major depression resembles that of the TCAsresembles that of the TCAs
.
Mechanism of Action
SSRI’sSSRI’s** FluoxetineFluoxetine )Prozac) )Prozac)
prototype of SSRIsprototype of SSRIs **SertralineSertraline
**ParoxetineParoxetine **FluvoxamineFluvoxamine
**CitalopramCitalopram ** EscitalopramEscitalopram
1 -SSRIs are much safer in overdose than other antidepressants
2 -They lack many of the adverse effects of TCAs and MAOIs
No blocking actions at M or α1 receptors, H1 receptors
* Better side effect profile
Advantages of SSRIS
1 -GIT adverse effects are common : GIT upset , nervousness, insomnia
2 -Diminished sexual functions3 -Headache and sleep disturbances
4 -Long-term weight gain5 -CVS side effects are minimal
#Many side effects disappear after the adaptation phase, when the antidepressant
effects begin ( up to 6 weeks) . #Side effects and their durations are highly
individual and drug-specific .
Side effects
1 -Major depression, Generalized anxiety disorder
) GAD (and panic disorders2 -Obsessive-Compulsive Disorder3 -Some eating disorders (bulimia)
4 -Premenstrual syndrome5 -Anorexia nervosa
6 -Premature ejaculation
Therapeutic Uses
DrugDrug InteractionsInteractions
A dangerous pharmacoA dangerous pharmaco--
dynamic interaction maydynamic interaction may
occuroccur
when when fluoxetinefluoxetine is used with is used with
MAOIsMAOIs leading to theleading to the
serotonin syndromeserotonin syndrome
““Serotonin SyndromeSerotonin Syndrome””
Life-threatening condition resulting fromoverstimulation of serotonin receptors
This can occur when two antidepressants are taken together )multiple different mechanisms of serotonin elevation)
Symptoms: Autonomic instability ) BP , pulse, temperature) mental confusion, shivering
sweating, rigidity/hypertonia and diarrhea
.
*There must be a 'washout' period of
at least two weeks when switching
from one antidepressant drug to another )It is necessary to clear the system
completely of one drug before starting another
To minimize the risk of serotonin syndrome