MOOD DISORDERS -NANDU KRISHNA J

• Pervasive and sustained feeling tone• That is experienced internally• That influences a person’s behavior and

perception of the world.• Distinguished from affect – the external

expression of mood.

WHAT IS MOOD ??

• Mood disorders - are a group of clinical conditions characterized by

• Loss of that sense of control• A subjective experience of great distress.

• 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

TYPES OF MOOD DISORDERS• Unipolar disorders or Major Depressive disorder

(with only major depressive episodes)• Bipolar disorders(with both manic and

depressive episodes/ with manic episodes alone)Three additional categories of mood disorders• Cyclothymia(less severe form of BPD)• Dysthymia (less severe form of UPD)• Hypomania (episode of manic symptoms that does not meet the DSM-IV-TR criteria for manic episode)

MAJOR DEPRESSIVE DISORDER• occurs without a H/O manic, mixed, hypomanic

episode.• must last at least 2 weeks• experiences two major symptoms -depressed mood -loss of interest or pleasure

• 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.

EPIDEMIOLOGYIncidence and Prevalence• prevalance 5-17% • 10-20% of chronically ill medical outpatientsSex • Women : Men = 2:1Age • Mean age of MDD: 40 years but recently, the

incidence of MDD is increasing in <20 years of age –(alcohol and drug abuse)

Marital status• Poor interpersonal relationships• Divorced or separatedSocioeconomic and cultural factor• No correlation for MDDComorbidity• 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.• Worsen the progress and increase the risk of suicide

BIOLOGIC THEORIES• Neurochemical factors• Norepinephrine and Serotonin • sensitivity of β-adrenergic receptors and

clinical antidepressant responses direct role• Depletion of serotonin depression • SSRIs are effective in the treatment of

depression.• Dopamine ; Acetylcholine (Ach) ; Gamma-

Aminobutyric acid (GABA)

ETIOLOGY

• Genetic factors To identify specific susceptibility genes using

the molecular genetic methods.• Endocrine-HPA axis » HPA activity; hallmark of stress responses » Hypercortisolemia suggests central disturbances • Alteration in the sleep neurophysiology » premature loss of deep (slow wave) sleep » nocturnal arousal » REM latency, which persist after recovery of a depressive episode.

• Immunological disturbance lymphocyte proliferation; which produce CRF and IL-1.• Structural functional brain imaging abnormal hyper densities • Neuroanatomical considerations mood disorders involve pathology of brain mainly in regions like prefrontal cortex, anterior cingulate,hippocampus and the amygdala.

PSYCHOSOCIAL THEORIES• Psychoanalytic theory: loss of loved object• Behavioral theory: experience of uncontrollable events• Cognitive theory: negative expectationsSOCIOLOGICAL THEORY • Stressful life events

TYPES OF DEPRESSIONDepression with specific features ie; specifiers are:• Mild, moderate and severe• Single episode or recurrent• Chronic• With melancholic features• With psychotic features• With catatonic features• With atypical features• With postpartum onset• With seasonal pattern

• Severity: Mild, Moderate, or Severe level of functional impairment

• Single episode: single episode of major depression• Recurrent: 2 or more episodes of major depression• Chronic: full criteria for a major depressive

episode have been met continually for at least the past 2 years

• With melancholic features – 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.

CRITERIA FOR SPECIFIERS

• With psychotic features – accompanied by delusions or hallucination.

• With catatonic features – includes motor activity that involve either uncontrollable and purposeless movement or fixed and inflexible posture.

• With atypical features – 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 • With seasonal pattern – related to changes in

seasons and reduced exposure to sunlight

• Psychological tests• Dexamethasone suppression test• Toxicology screening test• ICD 10 criteria

DIAGNOSIS

Treatment directed towards several goals• First, the patient’s safety must be guaranteed• Second, a complete diagnostic evaluation of the

patient is necessary• Third, a treatment plan that addresses not only immediate symptoms but also the patients prospective well-being should be initiated.

TREATMENT

Hospitalization: first and critical decision » risk of suicide or homicide » grossly reduced ability to get food and shelter » the need for diagnostic procedures » history of rapidly progressing symptoms » rupture of patient’s usual support system

• Psychotherapy

• Pharmacotherapy

• Physical therapy

MEDICAL MANAGEMENT

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.• SIDE EFFECTS mainly sedation, anticholinergic

effects, postural hypotension, lowering of the seizure threshold and cardiotoxicity.

• 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)

• 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 serotonin syndrome.

MONOAMINE OXIDASE INHIBITORS (MOAIs) phenelzine (45-90 mg daily), tranylcypromine

(20-40 mg daily), moclobemide (300-600 mg daily)

• MOA: These drugs increase the availability of NTs at synaptic clefts by inhibiting metabolism of NE and serotonin.

• 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.

• This is due to accumulation of amines on the systemic circulation, causing a potentially fatal hypertensive crisis.

OTHER ANTIDEPRESSANTS• Venlafaxine (75-375 mg daily) • SNRIs(<150 mg)and SSRIs(>150 mg)• Contraindicated in children and adolescents• S/E include hypertension above 150 mg dose,

glaucoma, • Mirtazapine (15-45 mg daily) • Noradrenergic and specific serotonergic

antidepressant (NaSSA)• Superior to SSRIs and SNRIs• S/E include weight gain, somnolence, excess

sedation, dry mouth.

Physical therapies• Electroconvulsive; Vagal nerve stimulation• Photo therapy • Repetitive transcranial magnetic stimulation

Three short term psychotherapies• Cognitive psychotherapy • Interpersonal psychotherapy • Behavior therapyOther therapies include• Psychoanalytic therapy• 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• Abrupt or acute onset• Severe depression• Typical clinical features• Well adjusted pre-

morbid personality• Good response to

treatment

Poor prognostic factors

• Double depression• Co-morbid physical

disease, personality disorders or alcohol dependence

• Chronic ongoing stress• Poor drug compliance• Marked mood

incongruent features

PROGNOSIS

• 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.

• 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)

MANIA

• Bipolar I disorder -clinical course of one or manic episodes and,

sometimes, major depressive episode.• Mixed episode -a period of at least 1 week in which both a manic episode and a major depressive episode occur almost daily.• Bipolar II disorder -a variant of bipolar disorder characterised by episodes

of major depression and hypomania rather than mania

BIPOLAR DISORDERS: TYPES

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

EPIDEMIOLOGY

• Neurotransmitters and structural hypothesis excessive levels of norepinephrine and

dopamine, decreased serotonin• Genetic considerations• Psychodynamic theories: faulty family dynamics

ETIOLOGY

• 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.

CLINICAL FEATURES

• Psychotic features -delusions -hallucinations

• Other symptoms -over religiosity -over spending/expansive ideas -over familiarity/ disinhibition -appearance

TREATMENT

Somatic treatment• Antidepressants enhanced by a mood stabilizer• Lithium carbonate (serum level 0.5-1.0 mmol/L)• Antipsychotics like olanzapine, haloperidol,

quetiapine and risperidone• Other drugs like sodium valproate,

carbamazepine, benzodiazepine

Psychosocial treatment• Cognitive therapy• Interpersonal therapy• Psychoanalytic psychotherapy• Behavior therapy• Group therapy• Family and marital therapy

Other mood disorders include:• Cyclothymia • Dysthymia• Depressive disorder not otherwise specified Minor depressive disorder Recurrent brief depressive disorder Postpsychotic DD of schizophrenia Premenstrual dysphoric disorder• Bipolar disorder not otherwise specified Mixed anxiety-depressive disorder Atypical depression