Mood

Disorders
Bipolar Affecitve Disorder (type I and II)
• Depressive episode
• Manic and hypomanic episode
• Mixed episodes (in ICD 10)
Major depression
• Single episode
• Recurrent
Dysthymia
Cyclothymia
 DSM-5
• New category – Bipolar and related disorders:
– Bipolar disorder I and II
– Cyclothymia
– Substance/medication-Induced BP and related
disorder
– BP and related disorder due to another medical
condition
 Bipolar Affecitve Disorder
Epidemiology:
• Lifetime prevalecne -7%-17% (MDD)
- 0,7 – 1,4% (BP)
• Annual incidence
– 1,59% (Major depression)
– < 1% (BP: I – 0,6%, II – 0,8%)
• Greater prevalence of major depression –
women
• Manic episodes – more common in men
 Epidemiology
The onset:
• BP type I – mean age 18 (from 5 to 50)
• BP type II – mean age mid-20s
• Major depression – mean age 40 (from 20 to 50)

• >90% with single manic episode – will have

recurrent mood episodes
• 60% of manic episodes occur immediately
before a major depressive disorder
 Risk and Prognostic Factors (BP I)
• High income vs Low income countries – 1,4%
vs 0,7% prevalence
• Higher rates of bipolar type I in separated,
divorced or widowed individuals
• 10-fold increased risk of BP in individuals that
have family members suffering from BP I or II
 Suicide Risk
• In BP 15x higer than in general population (BP
I).
• BP I may account for ¼ of all completed
suicides

• 1/3 individuals with BP II had a suicide

attempt in their lifetime
 Functionality
• Full recovery between episodes
• Up to 30% show severe impairment in work
role function (BP I)
• In cognitive test – more poorly preformance
than general population
 Comorbidity
Higher risk of suffering from:
• Anxiety disorders (3/4 of
patients)
• Alcohol abuse or dependece
• Obsessive-compulsive disorder
(OCD)
• Conduct disorder
• ADHD
• Higher rates of untreated
medical condition
 Etiology
• Biological factors:
– Norepinephrine/serotonin/dopamin (lack of
efficiacy or hyperstimulation of the regulation)
– Hormonal regulation (thyroid axis activity/ growth
hormone/prolactin)
– Alterations of sleep neurophysiology
 Etiology
• Genetic factors
• Psychological factors:
– Life events and enviromental stress – even up to
50% of first episodes are related to life events
– Personality factors
What is Bipolar Affective Disorder?
• Repeated (i.e. at least 2) mood episodes
• In which mood and activity levels are
significantly disturbed (elevated or decreased)
• Recovery is usually complete between
episodes
• Incidence in the two sexes is more nearly
equal
 Mixed
Manic
Subclinical hypomania,
hypertymia Hypomania

Remission

Subclinical depression

Depression

Young et al. Practical management of bipolar disorder. Cambridge University

Press, 2010
 Incorrect and delayed diagnose
• 8,9 years latency to proper bipolar diagnose
• 9,6 years latency to proper treatment
(between episodes)
• 3,5 years of incorrect diagnose before the BP
• Conversion of the diagnose in 32,8%
• Average number of diagnoses 2,23
• Drug resistance due to incorrect diagnose
 Rapid cycling
• At least 4 episodes
(manic, depressive,
hypomanic, mixed)
during last 1 year
Spectrum of BP (Akiskal and Pinto)
• I – typical course with manic episodes
• I1/2 – depressions with chronic hypomanic
episode
• II – BP with hypomanic episodes
• II1/2 – depresive episodes, with
cyclothymic temperament
• III – recurrent depressive and hypomanic
episodes due to pharmacotherapy
(mainly antidepressive drugs)
Spectrum of BP (Akiskal and Pinto)
• III1/2 – recurrent hypomanic episodes due
to alcohol or other psychostimulants
abuse
• IV – depressive episodes, with
hyperthymic temperament
 Manic episode
• Mood is elevated (from carefree joviality to
almost uncontrollable excitement)
• Self-esteem is inflated / grandiosity,
• Decreased need for sleep
• Increase in goal-directed activity
• Pressure of speech or more talkative,
• Flight of ideas
• Distractability,
• Talkativeness (rapid, pressured, loud, difficult to
innterrupt speach)
• Excessive involvemnet in pleasurable activities
• Over-optimistic ideas,
• Perceptual disorders may occur (appreciation of
colours as especially vivid, preoccupation with fine
details of surfaces or textures)
• Spending money recklessly,
• Becoming aggressive, amorous
• Increased energy, resulting in overactivity,
• Attention cannot be sustained,
• Normal social inhibitions are lost.
At least 3 or more symptoms (4 if mood is only
irritable) for manic/hypomanic episode.
 Manic episode
• The episode should last for at least 1 week and
should be severe enough to disrupt ordinary
work and social activities more or less completely
• The first episode occurs most commonly between
the ages of 15 and 30 years
• DSM-5 – at least 3 or more of listed symptoms
present for manic/hypomanic
• If mood irritable or expansive – at least 4 of
criterion B needed
 Mania With Psychotic Symptoms

• Inflated self-esteem and grandiose ideas may

develop into delusions, and irritability and
suspiciousness into delusions of persecution
• Grandiose or religious delusions
• Aggression or violence
• Neglect of eating, drinking, and personal
hygiene
• Usually mood conguren delusions
 Hypomanic episode
• Lesser degree of mania for at least 4 days
• Mild elevation of mood (for at least several
days)
• Increased energy and goal-directed activity
• Usually marked feelings of well-being
• Physical and mental efficiency
• Irritability
• Concentration and attention may be impaired
• Decreased need for sleep
• Flight of ideas
• Increased sociability,
• Talkativeness,
• Overfamiliarity,
• Increased sexual energy,
• Not accompanied by delusional beliefs or
hallucinations
Often present but not to the extent that they
lead to disruption of work or result in social
rejection.
 Bipolar Disorder type II
• Common feature of BP II is impulsivity.
• Often starts with depressive episode (up to 12%)
• Higher number episodes than in BP I
• 5-15% individuals have multiple (>4) mood
episodes with in previous 1 year (rapid cycling)
• About 5-15% individual have coversion of
diagnose to BP I
• Rapid cycling is associated with a poor prognosis
 Mixed episodes
Fulfilled criteria of major depression
Coexistence of 2-3 manic or hypomanic
symptoms within a single depressive episode.

Fulfilled criteria of manic episode with few

depressive disorders
For DSM-5 – mixed episodes are coded in
specifiers
Patients mood and symptoms may alternate rapidly.
Major depressive episode and MDD
• Symptoms duration of at least 2 weeks

• Mean time of untreated major depression

episode is 6-24 months

• Three varieties:
– mild,
– moderate,
– and severe
 Symptoms
• Depressed mood
• Loss of interest and enjoyment
• Significant weight loss
• Psychomotor agitation or retardation
• Reduced energy leading to increased
fatiguability and diminished activity (97%)
• Ideas of guilt and unworthiness (even in a mild
type of episode);
 Other symptoms
• disturbed sleep (80%);
• reduced concentration and attention;
• recurrent thoughts of death;
• reduced self-esteem and self-confidence;
• black and pessimistic views of the future;
• ideas or acts of self-harm or suicide;
• tiredness after only slight effort
• diminished appetite.
DSM-5 - At least 5 of symptoms (1 of them lowered mood
or anhedonia)
 Severity od depression (ICD 10)
• Mild – at least 2 of the „main symtoms”
(anhedonia, anergia, lowered mood) and 2 other
symptoms for at least 2 weeks
• Moderate – at least 2 of the „main symptoms” and
3 (better 4) of the others for at least 2 weeks
• Severe – all 3 „main symptoms” and 4 other but at
a very severe level for at least 2 weeks, but in great
severity time criterium is not crusial
 Epidemiology of MDD
• 1,5-3 fold higher rates in females
• Different course – some individuals rarely
expereince remission, other have many years
• Recovery typically begins within:
– 3 months after onset for 2 in 5 individuals
– 1 year for 4 in 5
• Risk of recurrence lowers progressively with the
duration of remission
• Neuroticism is a risk factor for the onset of MDD
 Types of depression
• Typical/ melancholic
• Atypical
• Catatonic
• Masked
• Anxiety
• Psychotic
• Hipochondric
• Compulsive
 Atypical depression
• Somnolentia
• Weight gain, huge apetite
• Heavy limbs „like if they were lead made”
• Vulnerable to criticism
• Good reaction on positive experiences
(reactivness)
 Seasonal pattern
• Experience depression during particular
season
• Most commonly during winter
• Likely to respond to treatment with light
therapy
• Known also as seasonal affective disorder
(SAD)
 Masked mood change
• irritability
• excessive consumption of alcohol
• histrionic behaviour
• exacerbation of pre-existing phobic or
obsessional symptoms
• hypochondriacal preoccupations
• pain
 "somatic" symptoms
• loss of interest or pleasure in activities that are
normally enjoyable
• lack of emotional reactivity to normally
pleasurable surroundings and events
• waking in the morning 2 hours or more before
the usual time
• depression worse in the morning
• objective evidence of definite psychomotor
retardation or agitation
• marked loss of appetite; weight loss
 Psychotic Symptoms in Severe
Depressive Episode
• Delusions involve ideas of sin, poverty, or
imminent disasters, responsibility for which
may be assumed by the patient;
• Auditory or olfactory hallucinations are usually
of accusatory voices or of rotting filth or
decomposing flesh
 Major depressive disorder
• Repeated episodes of depression
• Without any history of independent episodes
of mood elevation and increased energy
• The first episode - at any age from childhood
to old age
• Mean lenth of episode – 6 months (3-12)
 BP MDD
Depressive and manic episodes Only depressive episodes

BP and MDD in family history Only MDD in family history

Cyclothymic, syntonic, extravertive Melancholic, anankastic, neurotic,

personality traits before the onset introvertive personality traits before the
onset
The same prevelecne in men and women Higher prevelance in women

Onset in 20-30s Onset after 40s

Average amount of episodes – 6-10 Average amount of episodes 3-4

Avereage time of episode – about 3 Average time of episode – 6-9 months or

months even longer
Clinical features: motor retardation, mild Severe anxiety, restlessness, motor
anxiety, hipersomnia agitation, delusions, insomnia
 Probability of diagnosis
• BP: • MDD:
• Hypersomnia/ naps during the day • Insomnia/ sleep reduction
• Hyperphagia/ gaining weigth
• Other atypical symptoms
• Loss of apatite and/or
• Psychomotor retardation loss of weight
• Psychotic symptoms and/or • Normal or inflated activity
patological guilt
• Emotional lability/ manic
• Somatic symptoms
symptoms • Later onset (>25)
• Early begining (<25)
• Long time of episodes
• Many of the depressive episodes
in the past (>5) (>6 months)
 What is Dysthymia?

A chronic depression of mood which does not

currently fulfill the criteria for recurrent
depressive disorder, mild or moderate severity
Periods of days or weeks when patients describe
themselves as well, but most of the time they
feel tired and depressed; everything is an
effort and nothing is enjoyed
Dysthymia – Persistent Depressive Disorder
2 or more of following:
• Poor apetite or overeating
• Sleep problems
• Low energy or fatigue
• Low self-esteem
• Poor concentration or difficulty in making decisions
• Feeling of hopelessness

Beginng in adult life and lasts for at least several

years (At least 2 years).
 Epidemiology
• Prevalence in USA – 0,5%

• Earlier onset (before age 21) is associated

with higher likehood of comorbid personality
disorders and substance use disorders
 Cyclothymia
• A persistent instability of mood, involving
numerous periods of mild depression and mild
elation.
• Patients never meet criteria for hypomania and
depression
• The diagnosis is difficult to establish without a
prolonged period of observation
• For at least 2 years (1 year for children and
adolescents)
• Symptoms free intervals – <2 months
 Epidemiology
• Prevalence – 0,4%-1%
• Male=female prevalence
• 15-50% individuals may develop BP I or II
Disruptive Mood Dysregulation Disorder
• DSM-5 diagnose:
– Severe recurent outbursts manifested verbally and/or
behaviorally – out of proportion in intensity or duration to
the situation
– Temper outbursts are inconsistent with developmental level
– 3 or more times a week
– With irritable or angry mood for most of a day, observable
by others
– Present for more than 12 months, with no more than 3
months without symptoms
– Present in at least 2 of 3 settings (home, school, with peers)
 Epidemiology
• Prevalence – 2%-5%
• Common among chlidren presenting to pediatric
mental health clinic
• Onset must be before 10 years
• Developmental age of at least 6 years
 Premenstrual Dysphoric Disorder
• In majority of menstrual cycles
• At least 5 of symptoms in the final week before
onset os menses
• Start to improve within a few days after onset
• Becomes minimal or absent in the week postmenses
 Premenstrual Dysphoric Disorder
• >1 must be present:
– Marked affective lability
– Marked irritability or anger or increased
interpersonal conflicts
– Marked depressed mood, feelings of
hopelessness
– Marked anxiety, tension, and/or fellings of being
keyed up or on edge
 Premenstrual Dysphoric Disorder
• Additionally >1 must be present to reach total of
5 symptoms:
• Decreased interest in usual activities
• Subjective difficulties in concentration
• Mareked lack of energy, easy fatigability
• Problems with sleep
• Being overwhelmed or out of control
• Physical symptoms like: breast tenderness or
swelling, joint or muscle pain, sensation of
„bloating”, or weight gain
 Treatment
• Hospitalization
• Psychotherapy
• Pharmacotherapy
• Electric shock therapy
 Indications for hospitalization
• High risk of suicide or homocide
• Patient’s grossly reduced ability to get food
and shelther
• Need for diagnostic procedures
• Also rapidly progressing symptoms
 Pharmacotherapy
• Antidepresant medications
• Antipsychotic medications
• Anticonvulsant medications
• Benzodiazepines
• Lithium
 Main aims of pharmacotherapy
• Achievement of as fastest and as full
therapeutic response and remission as
possible
• Prevension of an early relapse
• Full remission without any residual symptoms
• Fully recovering the social functioning of the
patient
 The factors that infulence the drug
choice
• In the previous episodes:
– Effectiveness
– Tolerance
– Adverse effects
• Comorbidity
• The profile of adverse effects
• Safety of drug due to other somatic diseases
• Other drugs used (possible interactions)
The factors that infulence the drug
choice
• Present symptoms
• Compliance/noncompliance
• Doctor’s experience with the drug
• Availability of the drug and the price
 Antidepresants
• NE Reuptake Inhibitors (NRI) – nortriptyline,
maprotiline, reboxetine, amoxetine
• 5-HT reuptake Inhibitors (SSRI)– citalopram,
escitalopram, fluoxetine, fluvoxamine,
paroxetine, sertaline
• NE and 5-HT reuptake inhibitors (SNRI)–
amitriptyline, doxepin, imipramine, venlafaxine
• Pre- and postsynaptic active agents –
nefazodone,
 Antidepresants
• Norepinephrine and Dopamine Reuptake Inhibitors
(NDRI) – bupropion
• Noradrenergic and Specific Serotonergic
Antidepressant (NaSSA) – mirtazapine
• Serotonin Agonist and Reuptake Inhibitors (SARI) –
trazodone
• Inhibitors of Monoamine Oxidase (IMAO) –
moclobemid, selegiline
• Tricyclic antidepresive drugs – clomipramine,
amitryptyline dezipramine, imipramine
 Clinical features of depression and
choice of antidepressants
Apathy, social Anxiety, Compulsions, agitation Depression Depression
withdrawal, social phobia, obsessions with with pain
lack of mixed anxiety insomnia
motivation disorders

Bupropion, SSRI, Klomipramine Mirtazapine, Agomelatine, Duloksetine,

venlafaxine, venlafaxine SSRI, mianserine, mianserine, venlafaxine,
sertraline, agomelatine, venlafaxine trazodon, mirtazapine, amitryptyline,
reboksetine, tianeptine, amitryptyline, trazodon, milnacipran
milnacipran, moklobemid doksepine, doksepine
moclobemid klomipramine
 Drug choice in depression
Type of depression I choice II choice III choice
With restlessness SNRI(mirtazapine) SARISSRIothers TCA
(agitated) mianserine
SARIIMAO
SSRIothers
With insomnia agomelatine, mianserine, others TCA
mirtazapine, SARI
Dystymia SSRItianeptine TLPD SNRI
IMAOmianserine

With compulsions klomipramine, Other SSRI potiencialization

paroxetine
In BP Mood stabilazers SSRI SNRI, others TCA

In the course of somatic duloksetine, SSRI IMAO, tianeptineSNRI mianserineTCA

disease
atypical SSRI, IMAO IMAO, tianeptine, TCA
mianserine
 Antidepresants – side effects
• Dry mouth
• Urinary retention
• Blurred vision
• Constipation
• Sedation
• Sleep disruption
• Weight gain
 Antidepresants – side effects
• Headache
• Nausea
• Gastrointestinal disturbance/diarrhea
• Abdominal pain
• Inability to achieve an erection
• Inability to achieve an orgasm
• Loss of libido
• Agitation
 Antipsychotics
• Olanzapine
• Risperidone
• Quetiapine
• Aripiprazole
• Clozapine
• Ziprazidone
 Anticonvulsants
• Lamotrigine
• Valproic acid
• Carbamazepine
• Topiramate
 Anticonvulsants – side effects
• Liver and kidney damage
• Dizziness
• Drowsiness
• Nausea
• Tremor
• Rash
• Weight gain
 Acute mania treatment in BD I
• First line drugs:
• Lithium, olanzapine, quetiapine, risperidon, aripiprazole,
zaiprasidone or complex therapy
• Second line:
• Carbamazepine, ECT,
• Third line:
• Haloperidol, chlorpromazine, clozapine or complex
therapy
• Not recommended:
• Monotherapy with gabapentin, topiramate, lamotrigine
Acute depression treatment in BD I
• First line drugs:
• Lithium, lamotrigine, quetiapine + SSRI, olanzapine +
SSRI, lithium + bupropion
• Second line:
• Quetiapine + SSRI, lithium + lamotrigine
• Third line:
• Carbamazepine, olanzapine, lithium + carbamazepine,
lithium + venlafaxine, lithium +MAOI, ECT, lithium + TCA
• Not recommended:
• Gabapentin or aripiprazole monotherapy
Acute depression treatment in BD II
• First line drugs:
• Quetiapine
• Second line:
• Lithium, lamotrigine, lithium + antidepressants, atypical
antipsychotics + antidepressants
• Third line:
• Antidepressants monotherapy, switch to alternate
antidepressant, ziprasidone
 Drug resistancy in depression
• 4-6 weeks treatment then optimalization of
the dose (the maximum dose for 4-6 weeks)
• If no response change the drug into another
or add a second one or use potentialization
• If those acctions will bring no effect go with
the ECT
Potentialization of antidepressants
• Lithium > triiodothyronine, atypical antipsychotic
drug (best efficacy)
• Other possible:
– Anticonvulsant drugs,
– Tyroxine,
– Buspiron,
– Modafinil,
– Pindolol,
– Dopaminergic substances (amantadine)
– Zink
– Estrogenes
– Folic acid and B12
 Responce to the treatment
Responce:
reducing the intensity of deressive symptoms
by at least 50% (50-74%) compared to the
start point assessed by following sclaes:
• HDRS
• MADRS
• BDI
• CGI
 Reaction to the treatment
• Improvement – reduced intensity of
depressive symptoms by 20-30%
• Response
• Remission (more than 75%):
– Full
– With residual symptoms
 Factors that influence the
treatment

A. Adequacy of treatment
B. Behavioral reinforces – external
factors that sustain the symptoms
C. Compliance
D. Diagnosis
 Adequacy of treatment
• Adequate choice of the drug
• Adequate dose
• Adequate durance of treatment
• Adequate concentration of the drug in the
blood (fast vs slow metabolizers)
• Strategies of increasement of efficacy
• Psychoeducation and building relationship
with the patient
 Behavioral reinforces
• Losses in patients life
• Lifetime events that need adaptation
• Life summary
• Family and partnership problems
• Secondary benefits from the disorder
• Symptoms as elemtent of control over the
enviroment
 Compliance
• 40% of patients stop using the drugs in the
first 30 days
• Next 30% of patients in following 60 days
 Diagnosis
• Coexisitng other somatic diseases
(hypothyreoidosis)
• B12 and folic acid insufficiency
• Comorbidity of other disorders (personality
disorders, substance abuse, anxiety disorders)
 Clinical steps in treatment

Profilacitve
Treatment of Sustaining treatment
acute phase treatment
Avoiding relapses

6-12 At least
weeks 6 months > 1 year

Patients with 2 or more episodes in the past

should continue phamracotherapy for at least 2
years
 Common mistakes in therapy
• Benzodiazepines as first line therapy
• Too low doses, too short time of admission of
drugs
• Not informing the patient about the time
needed to achevie effectivness of drugs
• Not avoiding the drug interactions