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MOOD DISORDERS
-NANDU KRISHNA J
ā€¢ Pervasive and sustained feeling tone
ā€¢ That is experienced internally
ā€¢ That influences a personā€™s behavior and
perception of the world.
ā€¢ Distinguished from affect ā€“ the external
expression of mood.
ā€¢ Mood disorders - are a group of clinical conditions
characterized by
ā€¢ Loss of that sense of control
ā€¢ A subjective experience of great distress.
ā€¢ Importance : virtually always impair interpersonal, social and
occupational functioning
Elevated mood Depressed mood Others
expansiveness Lack of energy / interest Change in activity level
Flight of ideas Feeling of guilt Change in cognitive
abilities
Decreased sleep Difficulty of concentration Change in speech
Grandiose ideas Loss of appetite Change in biological
functions
Thoughts of death/ suicide
ā€¢ Unipolar disorders or Major Depressive disorder
(with only major depressive episodes)
ā€¢ Bipolar disorders(with both manic and
depressive episodes/ with manic episodes alone)
Three additional categories of mood disorders
ā€¢ Cyclothymia(less severe form of BPD)
ā€¢ Dysthymia (less severe form of UPD)
ā€¢ Hypomania (episode of manic
symptoms that does not meet the
DSM-IV-TR criteria for manic episode)
ā€¢ occurs without a H/O manic, mixed, hypomanic
episode.
ā€¢ must last at least 2 weeks
ā€¢ experiences two major symptoms
-depressed mood
-loss of interest or pleasure
ā€¢ And also experiences at least four symptoms that
includes:
-changes in appetite and weight,
-changes in sleep and activity,
-psychomotor agitation or retardation,
-lack of energy,
-feelings of worthlessness or inappropriate guilt,
-problems thinking and making decisions,
-recurring thoughts of death or suicide.
Incidence and Prevalence
ā€¢ prevalance 5-17%
ā€¢ 10-20% of chronically ill medical outpatients
Sex
ā€¢ Women : Men = 2:1
Age
ā€¢ Mean age of MDD: 40 years but recently, the
incidence of MDD is increasing in <20 years of
age ā€“(alcohol and drug abuse)
Marital status
ā€¢ Poor interpersonal relationships
ā€¢ Divorced or separated
Socioeconomic and cultural factor
ā€¢ No correlation for MDD
Comorbidity
ā€¢ Increased risk of having one or
more additional comorbid Axis I
disorders like alcohol abuse or
dependence, panic disorder,
obsessive compulsive disorder,
social anxiety disorder.
ā€¢ Worsen the progress and increase the risk of
suicide
BIOLOGIC THEORIES
ā€¢ Neurochemical factors
ā€¢ Norepinephrine and Serotonin
ā€¢ sensitivity of Ī²-adrenergic receptors and
clinical antidepressant responses direct role
ā€¢ Depletion of serotonin depression
ā€¢ SSRIs are effective in the treatment of
depression.
ā€¢ Dopamine ; Acetylcholine (Ach) ; Gamma-
Aminobutyric acid (GABA)
ā€¢ Genetic factors
To identify specific susceptibility genes using
the molecular genetic methods.
ā€¢ Endocrine-HPA axis
Ā» HPA activity; hallmark of stress responses
Ā» Hypercortisolemia suggests central disturbances
ā€¢ Alteration in the sleep neurophysiology
Ā» premature loss of deep (slow wave) sleep
Ā» nocturnal arousal
Ā» REM latency, which
persist after recovery
of a depressive episode.
ā€¢ Immunological disturbance
lymphocyte proliferation; which
produce CRF and IL-1.
ā€¢ Structural functional brain imaging
abnormal hyper densities
ā€¢ Neuroanatomical considerations
mood disorders involve
pathology of brain mainly in
regions like prefrontal cortex,
anterior cingulate,hippocampus
and the amygdala.
PSYCHOSOCIAL THEORIES
ā€¢ Psychoanalytic theory:
loss of loved object
ā€¢ Behavioral theory:
experience of uncontrollable
events
ā€¢ Cognitive theory:
negative expectations
SOCIOLOGICAL THEORY
ā€¢ Stressful life events
Depression with specific features ie; specifiers are:
ā€¢ Mild, moderate and severe
ā€¢ Single episode or recurrent
ā€¢ Chronic
ā€¢ With melancholic features
ā€¢ With psychotic features
ā€¢ With catatonic features
ā€¢ With atypical features
ā€¢ With postpartum onset
ā€¢ With seasonal pattern
ā€¢ Severity: Mild, Moderate, or Severe level of
functional impairment
ā€¢ Single episode: single episode of major depression
ā€¢ Recurrent: 2 or more episodes of major depression
ā€¢ Chronic: full criteria for a major depressive
episode have been met continually for at least the
past 2 years
ā€¢ With melancholic features ā€“ severe depression
with lack to do something that used to bring
pleasure and associated with early morning
awakening, worsened mood in the morning, major
changes in appetite, and feelings of guilt, agitation.
ā€¢ With psychotic features ā€“ accompanied by
delusions or hallucination.
ā€¢ With catatonic features ā€“ includes motor activity
that involve either uncontrollable and purposeless
movement or fixed and inflexible posture.
ā€¢ With atypical features ā€“ includes the ability to be
cheered by happy events, increased appetite,
excessive need for sleep, sensitivity to rejection,
and a heavy feeling in arms or legs.
ā€¢ With peripartum onset
ā€¢ With seasonal pattern ā€“ related to changes in
seasons and reduced exposure to sunlight
ā€¢ Psychological tests
ā€¢ Dexamethasone suppression test
ā€¢ Toxicology screening test
ā€¢ ICD 10 criteria
Treatment directed towards several goals
ā€¢ First, the patientā€™s safety must be guaranteed
ā€¢ Second, a complete diagnostic evaluation of the
patient is necessary
ā€¢ Third, a treatment plan
that addresses not only
immediate symptoms
but also the patients
prospective well-being
should be initiated.
Hospitalization: first and critical decision
Ā» risk of suicide or homicide
Ā» grossly reduced ability to get food and shelter
Ā» the need for diagnostic procedures
Ā» history of rapidly progressing symptoms
Ā» rupture of patientā€™s usual support system
ā€¢ Psychotherapy
ā€¢ Pharmacotherapy
ā€¢ Physical therapy
TRICYCLIC ANTIDEPRESSANTS
Amitriptyline(75-150 mg daily), Imipramine(75-
150 mg daily), Clomipramine (75-150 mg daily)
ā€¢ MOA: They inhibit the re-uptake of the amines
norepinephrine and serotonin at synaptic clefts.
ā€¢ SIDE EFFECTS mainly sedation, anticholinergic
effects, postural hypotension, lowering of the
seizure threshold and cardiotoxicity.
ā€¢ TCAs may be dangerous in overdose and in
people who have coexisting heart disease,
glaucoma and prostatism.
Pharmacotherapy
SELECTIVE SEROTONIN REUPTAKE INHIBITORS
citalopram (20-40 mg daily), fluoxetine (20-60
mg daily), sertaline (50-100 mg daily)
ā€¢ These are less cardiotoxic and sedative than
TCAs, and fewer anticholinergic effects.
ā€¢ They are safer in overdose, but can still cause
headache, nausea, anorexia and sexual
dysfunction.
ā€¢ Interact with other drugs increasing serotonin
to produce serotonin syndrome.
MONOAMINE OXIDASE INHIBITORS (MOAIs)
phenelzine (45-90 mg daily), tranylcypromine
(20-40 mg daily), moclobemide (300-600 mg
daily)
ā€¢ MOA: These drugs increase the availability of NTs
at synaptic clefts by inhibiting metabolism of NE
and serotonin.
ā€¢ They can cause potentially dangerous
interactions with drugs such as amphetamines,
and foods rich in tyramine such as cheese and red
wine called cheese reaction.
ā€¢ This is due to accumulation of amines on the
systemic circulation, causing a potentially fatal
hypertensive crisis.
OTHER ANTIDEPRESSANTS
ā€¢ Venlafaxine (75-375 mg daily)
ā€¢ SNRIs(<150 mg)and SSRIs(>150 mg)
ā€¢ Contraindicated in children and adolescents
ā€¢ S/E include hypertension above 150 mg dose,
glaucoma,
ā€¢ Mirtazapine (15-45 mg daily)
ā€¢ Noradrenergic and specific serotonergic
antidepressant (NaSSA)
ā€¢ Superior to SSRIs and SNRIs
ā€¢ S/E include weight gain, somnolence, excess
sedation, dry mouth.
Physical therapies
ā€¢ Electroconvulsive; Vagal nerve stimulation
ā€¢ Photo therapy
ā€¢ Repetitive transcranial magnetic stimulation
Three short term psychotherapies
ā€¢ Cognitive psychotherapy
ā€¢ Interpersonal psychotherapy
ā€¢ Behavior therapy
Other therapies include
ā€¢ Psychoanalytic therapy
ā€¢ Marital and family therapy
Psychosocial therapies
TCA OR SSRI
Depending on physician preference
Failed trial due to response or
rate-limiting adverse effect
Partial
response
Cross to alternative
agent (TCA or SSRI)
Either switch to alternative
agent or attempt augmentation
Failed trial
Trial of second line agent with evidence
of activity in TCA nonresponders.
Alternatively treat with ECT.
Full remission
Maintain as
described above
Maintain treatment
for at least 4-6
months in case of first
time episode; longer
in case of recurrent
disease
Full remission
Algorithm
for treating
patient
with MDD
Uncomplicated, physically healthy outpatient without
any contraindication to a specific class of antidepressant
Good prognostic factors
ā€¢ Abrupt or acute onset
ā€¢ Severe depression
ā€¢ Typical clinical features
ā€¢ Well adjusted pre-
morbid personality
ā€¢ Good response to
treatment
Poor prognostic factors
ā€¢ Double depression
ā€¢ Co-morbid physical
disease, personality
disorders or alcohol
dependence
ā€¢ Chronic ongoing stress
ā€¢ Poor drug compliance
ā€¢ Marked mood
incongruent features
ā€¢ A hypomanic episode:
lasts at least 4 days similar to a manic episode
except that it is not sufficiently severe to cause
impairment in social or occupational functioning,
and no psychotic features are present.
ā€¢ A manic episode:
is a distinct period of an
abnormally and persistently
elevated, expansive, or
irritable mood lasting for at
least 1 week(or less if the
patient is hospitalized)
ā€¢ Bipolar I disorder
-clinical course of one or manic episodes and,
sometimes, major depressive episode.
ā€¢ Mixed episode
-a period of at least 1 week in
which both a manic episode
and a major depressive
episode occur almost daily.
ā€¢ Bipolar II disorder
-a variant of bipolar disorder characterised by
episodes of major depression and hypomania
rather than mania
Incidence and Prevalence
a lifetime prevalence of 1-2%
Sex
Women : Men ratio 1:1 (BPD1)
Age
Mean age of BPD is 20 years
ie; late adolescent or early adulthood
(18 for BPD 1 and 22 for BPD 2)
Socioeconomic and cultural factors
BPD 1: upper socioeconomic group
ā€¢ Neurotransmitters and structural hypothesis
excessive levels of norepinephrine and
dopamine, decreased serotonin
ā€¢ Genetic considerations
ā€¢ Psychodynamic theories:
faulty family dynamics
ā€¢ Core features
- elevated/irritable mood includes
euphoria(grade 1), elation(grade 2),
exaltation(grade 3), ecstasy(grade 4).
- increased speech associated with volubility,
acceleration, pressured speech-difficult to
interrupt
- decreased need for sleep
- increased psychomotor activity like over
activity / restlessness, excitement, stupor.
ā€¢ Psychotic features
-delusions
-hallucinations
ā€¢ Other symptoms
-over religiosity
-over spending/expansive ideas
-over familiarity/ disinhibition
-appearance
Somatic treatment
ā€¢ Antidepressants enhanced
by a mood stabilizer
ā€¢ Lithium carbonate (serum level 0.5-1.0 mmol/L)
ā€¢ Antipsychotics like olanzapine, haloperidol,
quetiapine and risperidone
ā€¢ Other drugs like sodium valproate,
carbamazepine, benzodiazepine
Psychosocial treatment
ā€¢ Cognitive therapy
ā€¢ Interpersonal therapy
ā€¢ Psychoanalytic psychotherapy
ā€¢ Behavior therapy
ā€¢ Group therapy
ā€¢ Family and marital therapy
Other mood disorders include:
ā€¢ Cyclothymia
ā€¢ Dysthymia
ā€¢ Depressive disorder not otherwise specified
Minor depressive disorder
Recurrent brief depressive disorder
Postpsychotic DD of schizophrenia
Premenstrual dysphoric disorder
ā€¢ Bipolar disorder not otherwise specified
Mixed anxiety-depressive disorder
Atypical depression
Mood disorders:major depressive and bipolar disorder

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Mood disorders:major depressive and bipolar disorder

  • 2. ā€¢ Pervasive and sustained feeling tone ā€¢ That is experienced internally ā€¢ That influences a personā€™s behavior and perception of the world. ā€¢ Distinguished from affect ā€“ the external expression of mood.
  • 3. ā€¢ Mood disorders - are a group of clinical conditions characterized by ā€¢ Loss of that sense of control ā€¢ A subjective experience of great distress. ā€¢ Importance : virtually always impair interpersonal, social and occupational functioning Elevated mood Depressed mood Others expansiveness Lack of energy / interest Change in activity level Flight of ideas Feeling of guilt Change in cognitive abilities Decreased sleep Difficulty of concentration Change in speech Grandiose ideas Loss of appetite Change in biological functions Thoughts of death/ suicide
  • 4. ā€¢ Unipolar disorders or Major Depressive disorder (with only major depressive episodes) ā€¢ Bipolar disorders(with both manic and depressive episodes/ with manic episodes alone) Three additional categories of mood disorders ā€¢ Cyclothymia(less severe form of BPD) ā€¢ Dysthymia (less severe form of UPD) ā€¢ Hypomania (episode of manic symptoms that does not meet the DSM-IV-TR criteria for manic episode)
  • 5. ā€¢ occurs without a H/O manic, mixed, hypomanic episode. ā€¢ must last at least 2 weeks ā€¢ experiences two major symptoms -depressed mood -loss of interest or pleasure
  • 6. ā€¢ And also experiences at least four symptoms that includes: -changes in appetite and weight, -changes in sleep and activity, -psychomotor agitation or retardation, -lack of energy, -feelings of worthlessness or inappropriate guilt, -problems thinking and making decisions, -recurring thoughts of death or suicide.
  • 7. Incidence and Prevalence ā€¢ prevalance 5-17% ā€¢ 10-20% of chronically ill medical outpatients Sex ā€¢ Women : Men = 2:1 Age ā€¢ Mean age of MDD: 40 years but recently, the incidence of MDD is increasing in <20 years of age ā€“(alcohol and drug abuse)
  • 8. Marital status ā€¢ Poor interpersonal relationships ā€¢ Divorced or separated Socioeconomic and cultural factor ā€¢ No correlation for MDD Comorbidity ā€¢ Increased risk of having one or more additional comorbid Axis I disorders like alcohol abuse or dependence, panic disorder, obsessive compulsive disorder, social anxiety disorder. ā€¢ Worsen the progress and increase the risk of suicide
  • 9. BIOLOGIC THEORIES ā€¢ Neurochemical factors ā€¢ Norepinephrine and Serotonin ā€¢ sensitivity of Ī²-adrenergic receptors and clinical antidepressant responses direct role ā€¢ Depletion of serotonin depression ā€¢ SSRIs are effective in the treatment of depression. ā€¢ Dopamine ; Acetylcholine (Ach) ; Gamma- Aminobutyric acid (GABA)
  • 10. ā€¢ Genetic factors To identify specific susceptibility genes using the molecular genetic methods. ā€¢ Endocrine-HPA axis Ā» HPA activity; hallmark of stress responses Ā» Hypercortisolemia suggests central disturbances ā€¢ Alteration in the sleep neurophysiology Ā» premature loss of deep (slow wave) sleep Ā» nocturnal arousal Ā» REM latency, which persist after recovery of a depressive episode.
  • 11. ā€¢ Immunological disturbance lymphocyte proliferation; which produce CRF and IL-1. ā€¢ Structural functional brain imaging abnormal hyper densities ā€¢ Neuroanatomical considerations mood disorders involve pathology of brain mainly in regions like prefrontal cortex, anterior cingulate,hippocampus and the amygdala.
  • 12. PSYCHOSOCIAL THEORIES ā€¢ Psychoanalytic theory: loss of loved object ā€¢ Behavioral theory: experience of uncontrollable events ā€¢ Cognitive theory: negative expectations SOCIOLOGICAL THEORY ā€¢ Stressful life events
  • 13. Depression with specific features ie; specifiers are: ā€¢ Mild, moderate and severe ā€¢ Single episode or recurrent ā€¢ Chronic ā€¢ With melancholic features ā€¢ With psychotic features ā€¢ With catatonic features ā€¢ With atypical features ā€¢ With postpartum onset ā€¢ With seasonal pattern
  • 14. ā€¢ Severity: Mild, Moderate, or Severe level of functional impairment ā€¢ Single episode: single episode of major depression ā€¢ Recurrent: 2 or more episodes of major depression ā€¢ Chronic: full criteria for a major depressive episode have been met continually for at least the past 2 years ā€¢ With melancholic features ā€“ severe depression with lack to do something that used to bring pleasure and associated with early morning awakening, worsened mood in the morning, major changes in appetite, and feelings of guilt, agitation.
  • 15. ā€¢ With psychotic features ā€“ accompanied by delusions or hallucination. ā€¢ With catatonic features ā€“ includes motor activity that involve either uncontrollable and purposeless movement or fixed and inflexible posture. ā€¢ With atypical features ā€“ includes the ability to be cheered by happy events, increased appetite, excessive need for sleep, sensitivity to rejection, and a heavy feeling in arms or legs. ā€¢ With peripartum onset ā€¢ With seasonal pattern ā€“ related to changes in seasons and reduced exposure to sunlight
  • 16. ā€¢ Psychological tests ā€¢ Dexamethasone suppression test ā€¢ Toxicology screening test ā€¢ ICD 10 criteria
  • 17. Treatment directed towards several goals ā€¢ First, the patientā€™s safety must be guaranteed ā€¢ Second, a complete diagnostic evaluation of the patient is necessary ā€¢ Third, a treatment plan that addresses not only immediate symptoms but also the patients prospective well-being should be initiated.
  • 18. Hospitalization: first and critical decision Ā» risk of suicide or homicide Ā» grossly reduced ability to get food and shelter Ā» the need for diagnostic procedures Ā» history of rapidly progressing symptoms Ā» rupture of patientā€™s usual support system
  • 20. TRICYCLIC ANTIDEPRESSANTS Amitriptyline(75-150 mg daily), Imipramine(75- 150 mg daily), Clomipramine (75-150 mg daily) ā€¢ MOA: They inhibit the re-uptake of the amines norepinephrine and serotonin at synaptic clefts. ā€¢ SIDE EFFECTS mainly sedation, anticholinergic effects, postural hypotension, lowering of the seizure threshold and cardiotoxicity. ā€¢ TCAs may be dangerous in overdose and in people who have coexisting heart disease, glaucoma and prostatism. Pharmacotherapy
  • 21. SELECTIVE SEROTONIN REUPTAKE INHIBITORS citalopram (20-40 mg daily), fluoxetine (20-60 mg daily), sertaline (50-100 mg daily) ā€¢ These are less cardiotoxic and sedative than TCAs, and fewer anticholinergic effects. ā€¢ They are safer in overdose, but can still cause headache, nausea, anorexia and sexual dysfunction. ā€¢ Interact with other drugs increasing serotonin to produce serotonin syndrome.
  • 22.
  • 23. MONOAMINE OXIDASE INHIBITORS (MOAIs) phenelzine (45-90 mg daily), tranylcypromine (20-40 mg daily), moclobemide (300-600 mg daily) ā€¢ MOA: These drugs increase the availability of NTs at synaptic clefts by inhibiting metabolism of NE and serotonin. ā€¢ They can cause potentially dangerous interactions with drugs such as amphetamines, and foods rich in tyramine such as cheese and red wine called cheese reaction. ā€¢ This is due to accumulation of amines on the systemic circulation, causing a potentially fatal hypertensive crisis.
  • 24. OTHER ANTIDEPRESSANTS ā€¢ Venlafaxine (75-375 mg daily) ā€¢ SNRIs(<150 mg)and SSRIs(>150 mg) ā€¢ Contraindicated in children and adolescents ā€¢ S/E include hypertension above 150 mg dose, glaucoma, ā€¢ Mirtazapine (15-45 mg daily) ā€¢ Noradrenergic and specific serotonergic antidepressant (NaSSA) ā€¢ Superior to SSRIs and SNRIs ā€¢ S/E include weight gain, somnolence, excess sedation, dry mouth.
  • 25. Physical therapies ā€¢ Electroconvulsive; Vagal nerve stimulation ā€¢ Photo therapy ā€¢ Repetitive transcranial magnetic stimulation Three short term psychotherapies ā€¢ Cognitive psychotherapy ā€¢ Interpersonal psychotherapy ā€¢ Behavior therapy Other therapies include ā€¢ Psychoanalytic therapy ā€¢ Marital and family therapy Psychosocial therapies
  • 26. TCA OR SSRI Depending on physician preference Failed trial due to response or rate-limiting adverse effect Partial response Cross to alternative agent (TCA or SSRI) Either switch to alternative agent or attempt augmentation Failed trial Trial of second line agent with evidence of activity in TCA nonresponders. Alternatively treat with ECT. Full remission Maintain as described above Maintain treatment for at least 4-6 months in case of first time episode; longer in case of recurrent disease Full remission Algorithm for treating patient with MDD Uncomplicated, physically healthy outpatient without any contraindication to a specific class of antidepressant
  • 27. Good prognostic factors ā€¢ Abrupt or acute onset ā€¢ Severe depression ā€¢ Typical clinical features ā€¢ Well adjusted pre- morbid personality ā€¢ Good response to treatment Poor prognostic factors ā€¢ Double depression ā€¢ Co-morbid physical disease, personality disorders or alcohol dependence ā€¢ Chronic ongoing stress ā€¢ Poor drug compliance ā€¢ Marked mood incongruent features
  • 28. ā€¢ A hypomanic episode: lasts at least 4 days similar to a manic episode except that it is not sufficiently severe to cause impairment in social or occupational functioning, and no psychotic features are present. ā€¢ A manic episode: is a distinct period of an abnormally and persistently elevated, expansive, or irritable mood lasting for at least 1 week(or less if the patient is hospitalized)
  • 29. ā€¢ Bipolar I disorder -clinical course of one or manic episodes and, sometimes, major depressive episode. ā€¢ Mixed episode -a period of at least 1 week in which both a manic episode and a major depressive episode occur almost daily. ā€¢ Bipolar II disorder -a variant of bipolar disorder characterised by episodes of major depression and hypomania rather than mania
  • 30. Incidence and Prevalence a lifetime prevalence of 1-2% Sex Women : Men ratio 1:1 (BPD1) Age Mean age of BPD is 20 years ie; late adolescent or early adulthood (18 for BPD 1 and 22 for BPD 2) Socioeconomic and cultural factors BPD 1: upper socioeconomic group
  • 31. ā€¢ Neurotransmitters and structural hypothesis excessive levels of norepinephrine and dopamine, decreased serotonin ā€¢ Genetic considerations ā€¢ Psychodynamic theories: faulty family dynamics
  • 32. ā€¢ Core features - elevated/irritable mood includes euphoria(grade 1), elation(grade 2), exaltation(grade 3), ecstasy(grade 4). - increased speech associated with volubility, acceleration, pressured speech-difficult to interrupt - decreased need for sleep - increased psychomotor activity like over activity / restlessness, excitement, stupor.
  • 33. ā€¢ Psychotic features -delusions -hallucinations ā€¢ Other symptoms -over religiosity -over spending/expansive ideas -over familiarity/ disinhibition -appearance
  • 34. Somatic treatment ā€¢ Antidepressants enhanced by a mood stabilizer ā€¢ Lithium carbonate (serum level 0.5-1.0 mmol/L) ā€¢ Antipsychotics like olanzapine, haloperidol, quetiapine and risperidone ā€¢ Other drugs like sodium valproate, carbamazepine, benzodiazepine
  • 35. Psychosocial treatment ā€¢ Cognitive therapy ā€¢ Interpersonal therapy ā€¢ Psychoanalytic psychotherapy ā€¢ Behavior therapy ā€¢ Group therapy ā€¢ Family and marital therapy
  • 36. Other mood disorders include: ā€¢ Cyclothymia ā€¢ Dysthymia ā€¢ Depressive disorder not otherwise specified Minor depressive disorder Recurrent brief depressive disorder Postpsychotic DD of schizophrenia Premenstrual dysphoric disorder ā€¢ Bipolar disorder not otherwise specified Mixed anxiety-depressive disorder Atypical depression

Editor's Notes

  1. Incidence and Prevalence prevalance of almost 5-17% Approximately 10-20% of chronically ill medical outpatients are afttected with MDD Sex Women : Men = 2:1 (MDD) ; Age Mean age of MDD is 40 years but recently, the incidence of MDD is increasing in <20 years of age ā€“(alcohol and drug abuse)
  2. Nor epinephrine and Serotonin are the 2 main NT most implicated in pathophysiology of mood disorders. Downregulation or decreased sensitivity of beta-adrenergic receptors and clinical antidepressant responses indicates a direct role for the noradrenergic system in depression. Depletion of serotonin could precipitate depression and also SSRIs are effective in the treatment of depression. Dopamine ; Acetylcholine (Ach) ; Gamma-Aminobutyric acid (GABA)
  3. Genetic factors Recently, the primary focus of genetic studies has been to identify specific susceptibility genes using the molecular genetic methods. Endocrine-HPA axis Increased HPA activity is the hallmark of stress responses and hypercortisolemia in depression suggests central disturbances like decreased inhibitory sertonin tone, increased drive from NE, Ach, CRH; or decreased feedback inhibition from hippocampus. Alteration in the sleep neurophysiology premature loss of deep (slow wave) sleep and an increase in the nocturnal arousal. This results in reduced REM latency, which persist after recovery of a depressive episode.
  4. Immunological disturbance decreased lymphocyte proliferation; which produce CRF(neuromodulator) and IL-1(which induce gene activity for glucocorticoid synthesis). Structural and functional brain imaging abnormal hyperdensities Neuroanatomical considerations mood disorders involve pathology of brain mainly in regions like prefrontal cortex, anterior cingulate, hippocampus and the amygdala.
  5. Melancholy-suggestive or expressive of sadness or depression of mind or spirit
  6. With psychotic features ā€“ accompanied by delusions or hallucination, which may involve personal adequacy or other negative themes. With catatonic features ā€“ includes motor activity that involve either uncontrollable and purposeless movement or fixed and inflexible posture. With atypical features ā€“ includes the ability to be cheered by happy events, increased appetite, excessive need for sleep, sensitivity to rejection, and a heavy feeling in arms or legs. With peripartum onset ā€“ occurs during pregnancy or in the weeks or months after delivery (postpartum) With seasonal pattern ā€“ related to changes in seasons and reduced exposure to sunlight
  7. TRICYCLIC ANTIDEPRESSANTS amitriptyline(75-150 mg daily), imipramine(75-150 mg daily), clomipramine (75-150 mg daily) MOA: They inhibit the re-uptake of the amines norepinephrine and serotonin at synaptic clefts. The therapeutic effect is noticeable within a week or two. SIDE EFFECTS, such as sedation, anticholinergic effects, postural hypotension, lowering of the seizure threshold and cardiotoxicity, can be troublesome during this period. TCAs may be dangerous in overdose and in people who have coexisting heart disease, glaucoma and prostatism.
  8. SELECTIVE SEROTONIN REUPTAKE INHIBITORS citalopram (20-40 mg daily), fluoxetine (20-60 mg daily), sertaline (50-100 mg daily) These are less cardiotoxic and sedative than TCAs, and fewer anticholinergic effects. They are safer in overdose, but can still cause headache, nausea, anorexia and sexual dysfunction. Interact with other drugs increasing serotonin to produce ā€˜serotonin syndromeā€™; which is a rare syndrome of neuromuscular hyperactivity, autonomic hyperactivity and agitation, and potentially seizures, hyperthermia, confusion and even death.
  9. MONOAMINE OXIDASE INHIBITORS (MOAIS) like phenelzine (45-90 mg daily), tranylcypromine (20-40 mg daily), moclobemide (300-600 mg daily) MOA: These drugs increase the availability of neurotransmitters at synaptic clefts by inhibiting metabolism of noradrenaline and serotonin. They can cause potentially dangerous interactions with drugs such as amphetamines, and foods rich in tyramine such as cheese and red wine. This is due to accumulation of amines on the systemic circulation, causing a potentially fatal hypertensive crisis. Newer antidepressants Venlafaxine (75-375 mg daily) (NRIs(<150 mg)and SSRIs(>150)) S/E include hypertension above 150 mg dose mirtazapine (15-45 mg daily) S/E include weight gain, and excess sedation
  10. cognitive psychotherapy; goal is to alleviate depressive episodes and prevent their recurrence by helping patients identify and test negative cognitions; develop alternate, flexible, and positive ways of thinking; and rehearse new cognitive and behavioral responses. interpersonal psychotherapy based on two assumptions. First, current interpersonal problems are likely to have their roots in early dysfunctional relationships. second., current interpersonal problems are likely involved in precipitating or perpetuating the current depressive symptoms. Behavior therapy includes teaching patients to function in the world in such a way that they receive positive reinforcement. Psychoanalytically oriented therapy aims at changing the patientā€™s personality structure or character, not simply to alleviate symptoms by improving the interpersonal trust; capacity for intimacy; coping mechanism; the capacity to grieve and the ability to experience a wide range of emotions. Marital and family therapy examines the role of the mood disordered member in the overall psychological well-being of the whole family; and als examines the role of the entire family in the maintainence of patientā€™s symptoms. Electro convulsive therapy (Vagal nerve stimulation); Use of left vagal nerve stimulation using an electronic device implanted in the skin; vagus nerve connects to the enteric nervous system and, when stimulated, may cause release of NT peptides. Photo therapy introduced in 1984 as a treatment for patients with OCD, seasonal depression and sleep disorders. Involves exposing the patient to a range of 1,500 to 10,000 lux or more, typically with a light box that sits on a table or desk. It decreases the irritability and dimished functioning. Repetitive transcranial magnetic stimulation by placing a magnetic coil over the patients head to generate a precisely localised electromagnetic pulse