Facultatea de medicina si farmacie “Ovidiu”

Constanta

Depression

Studenta Olaru (Lungu) Gabriela

Anul II Asistenta farmacie
2020
 Depression - definition
Depression is a mood disorder that causes a
persistent feeling of sadness and loss of
interest.
Also called major depressive disorder or
clinical depression, it affects feelings,
thinking and behaviour and can lead to a
variety of emotional and physical problems.
 Depression - Epidemiological Data
• depressive disorder affects one in five people in general medical practice.
• it is underdiagnosed, being confused with somatic disorders in 50% of cases.
• depressive disorder negatively influences the development of somatic diseases
and, in turn, can cause somatic and cerebral impairment.
• 5% - 15% of the adult population is diagnosed with depressive disorder
• 30% of the general population have depression, and after some studies 70% of the
general population have depression
• 25% - 35% of patients with untreated major depression commit suicide
• male to female ratio: 1/2
• the peak of morbidity is between 25 and 44 years.
• increasing the incidence of depression at young age
• depression will be the second public health issue since 2020
• increased anxiety rate in US adolescents
• depression is an important prognostic factor in chronic medical illness
• depression is a risk factor for cardio- and cerebrovascular diseases
Depression - Epidemiological
Data
Depressive mood Psychomotor
inhibition / restlessness

Depressive ideation
COGNITION

• Decreased interest and pleasure (anhedonia)

• Decreased vital energy
• Attention and memory difficulties
• Ideas of guilt and incapacity
• Decreased interest in personal protection
 Depression - symptoms
Typical symptoms of depressive disorder:
•sad (depressive) mood for most of the day, almost every day, not influenced by circumstances,
present continuously for at least the last two weeks;
•loss of interest or pleasure in activities that were normally enjoyable;
•asthenia, fatigue.
Additional symptoms commonly encountered in depressive disorder:
•loss of self-confidence;
•feelings of guilt, guilt, self-reproach;
•recurrent thoughts of death or suicide or any suicidal behavior;
•diminishing the capacity of concentration (indecision, hesitation);
•modification of psychomotor activity in the sense of psychomotor agitation or inhibition;
•sleep disorders, for example insomnia, hypersomnia, superficial sleep, non-distressing;
•changes in appetite in the sense of decreasing or increasing appetite, with corresponding changes in
weight (at least 5% compared to the previous month's weight).
Other symptoms encountered in depressive disorder with predominantly somatic allure:
•constipation which is a consequence of sedentarism, psychomotor inhibition or is a side effect of
antidepressants;
•headache accentuated in the morning or following stressful situations;
•osteoarticular pain, especially in the lower limbs or in the spinal-lumbar spine;
•changes in sexual instinct with marked decrease in libido;
•marked loss of appetite, weight loss (often defined as 5% of body weight or more, in the last month),
a symptom associated with depression that frequently creates differential diagnosis problems with
severe somatic disorders, being an important factor delaying the diagnosis of depressive disorder .
 Depression – clinical interview
EXPRESSION
•- attitude: - retractile, with inhibited behavior, difficult to cooperate;
•- vestimentation: negligence, dark colors
•- voice: low speech rate, laconic speech with latency in answers, whispering, descending voice
•- look/glance: - avoiding direct eye contact, looking at the floor;
•- pantomime: - depressive face (it transmits sadness); melancholy omega; accentuated folds, pantomime
diminished in intensity and amplitude;
•KNOWLEDGE FUNCTIONS (cognitive functions)
•-sensation: - cenestopathy; everything is gray, erased; lifeless;
•-perception: - diminished, faded (objects perceived pale, with few details)
•-attention: - diminished with the focus on the negative events of life, concentration and low persistence;
•-memory: - hypomnesia of fixation and evocation (by lack of concentration and persistence of attention)
• -selective hypermnesia for negative events from the past;
•- thinking: - bradypsychia, slow thinking, diminished ideological flow, recurring thoughts about death; ruminations
on the subject of the disease and on existential themes; systematic pessimism
• - low quantitative idea, ideas of guilt, guilt, uselessness, with sad, pessimistic content; suicidal
ideation;
• - hypochondriac delirium (cancer, syphilis, AIDS), Cotard delirium - delusional dysmorphophobic ideas
(denial, immortality, enormity)
•-imagination: - decreased imagination, arid and painful landscape
Depressive appearance
Depressive appearance
 Depression – clinical interview
AFFECTIVE-EMOTIONAL FUNCTIONS
•- MOOD: - negative, depressive, pathological sadness, anxiety; phobic disorders;
- feelings: - of guilt, of uselessness, incapacity, of ruin, feelings of slow
escape of time; decrease of pleasure for activities;
- emotions: - emotional lability, easy crying
- other: - alcohol or drug use;
•- motivation: - prolonged deliberation, difficult start in the act; indecision, hesitation;
•- the instincts: - the diminution of the food instinct sometimes until the total food refusal
• - exaggeration of the food instinct sometimes up to bulimia, polyphagia;
• - disorders in achieving sexual pleasure with sexual inhibition, diminished
sexual appetite, with disappearance of libido, orgasm, impotence;
• - disorders of the defense instinct with - exaggeration: irritability, irascibility
• - decline: indifference to danger,
suicidal behavior with dominant suicidal ideation, suicide attempt; pseudo-suicide /
parasuicide behavior
• - disorders of the maternal instinct with its diminution, until the perversion
of the instinct (abandonment of the child)
 Depression – clinical interview
Volition
•- will: - decrease of will, abulia; neglecting one's own person;
•- motor-driven: - bradykinesia, hypokinesis until stupor, melancholic raptus
•- sleep and dream disorders: - waking insomnia (terminal) (3-4 hours in the morning),
nightmares with a morbid character;
•-activity: -verbal communication (language) - hypoactivity, mutism; voice with a low tone, low
intensity, almost whispered; monotone voice; with latency in answers;
• - nonverbal communication: negligent clothing, disorderly clothing, in dark
colors, without clothing ornaments; depressive facies (melancholic omega), depressive,
retractable posture (rubbing his hands or resting his forehead with his hands); the gaze is
sad on the floor;
•SYNTHESIS FUNCTION:
•-consciousness: - hypokinesia to the stupor; impairment of the body schema
(cenestopathies, hypochondriac syndrome, Cotard syndrome);
•- personality: - temperament: melancholic;
• - character: - partially cooperative attitude; with disinterest towards one's
own person; social isolation or withdrawal; inactivity; withdrawal from the family;
 Depression - diagnosis
For a diagnosis of depression, at least 5 of the following symptoms are
required, for a continuous duration of at least two weeks:
(It is recommended: The severity of these symptoms should also be
considered. The following are guidelines that suggest the need to refer to a
specialist)
•Depression or irritability most of the time
•Loss or decrease of pleasure or interest in most activities, including those that
have been interesting or enjoyable previously.
•Significant changes in weight or appetite.
•Sleep - Sleep disturbance or hypersomnia.
•Psychomotor - Sensation of slow motion or constant restlessness.
•Tiredness, slowness, lack of energy.
•Feelings of worthlessness or excessive guilt on most days.
•Problems of thinking, concentration, creativity and decision-making capacity -
on most days.
•Thoughts of death or suicide (preference to be dead - ideas of suicide - choice
of methods - planning)
 Depression – diagnosis ICD
Diagnostic criteria for mild depressive episode (F32.0)
At least 2 of the 3 typical symptoms and at least 2 of the common symptoms are required for a
definite diagnosis. None of the symptoms should be particularly intense. The minimum duration
of the entire episode is approximately 2 weeks.

Diagnostic criteria for moderate depressive episode (F32.1)

At least 2 of the 3 typical symptoms mentioned above are required for a definite diagnosis and
at least 3 (preferably 4) of the common symptoms. Many symptoms can have a higher degree of
severity, which is not essential, if a wide range of symptoms is present. The minimum duration
of the entire episode is 2 weeks. A subject with a moderate depressive episode will usually have
considerable difficulties in continuing their social, professional or domestic activities.

Diagnostic criteria for severe depressive episode, without psychotic symptoms (F32.2)
In order to establish a diagnosis of certainty, all 3 symptoms characteristic of moderate
depressive episode will be present and, in addition, 4 or more common symptoms, some having
severe intensity. If major symptoms such as agitation or slowness are marked, the patient may
be refractory or unable to describe other symptoms in detail. The depressive episode usually
lasts for at least 2 weeks, but if the symptoms are particularly severe, with a very rapid onset,
the diagnosis can also be made for a duration of the episode less than 2 weeks. During the
severe depressive episode, the patient is unlikely to continue social, professional or household
activities.
 Depression - differential diagnostic
• Sadness – normal human feeling
• Mourning
• Dysthymia
• Adaptive disorder with depressive mood
• Anxiety depressive mixed disorder
• Bipolar affective disorder with current depressive episode
• Borderline personality disorder
• Affective disorder due to a general medical condition (organic
depression)
• Alcohol and drug use
• Dementia
• Psychosis
• Malingering
 Depression due to a general medical
condition
These illness may be accompanied by a depressive mood
(overlap with depression (causes depression or may accentuate it)
•ORGANIC DEPRESSION VS DEPRESSIVE DISORDER
•Parkinson (50-75% depression).
•Celiac disease
•lupus
•neurocysticercosis
•toxoplasmosis
•Lyme disease
•Encephalitis (West-Nile virus - 30% depression)
•Endocrinopathies – Addison disease, Cushing disease, Graves disease,
Thyroiditis
•Hashimoto, Hyperthyroidism, Hypothyroidism, Hypoparathyroidism
•Pituitary gland tumors, pancreas, lymphomas, CNS, lung, etc
•post-concusional syndrome , pseudobulbar palsy, cerebral ateromatosis
•Multiple sclerosis, interferon treatment, nutritional impairment
 Depression – clinical scales
• HAMILTON Depression Scale 17-26 items (M. Hamilton '1960)
Test duration: 20-30 minutes. Main indications: to determine the
severity of depression, used mainly in research in patients of any
age

• M.A.D.R.S. Scale (Montgomery-Asberg Scale)

10 items
The scale aims to study changes due to therapeutic effects. Includes
10 items listed in 6 intensity levels and captures changes in
treatment (hetero-evaluation).
 Depression - treatment
The Evolution of Antidepressants: Trend in
Development
Broad-spectrum agents More selective agents Novel agents affecting multiple
(multiple action) (single action) monoamine targets

1950s 1960s 1970s 1980s 1990s 2000+

Escitalopram
Imipramine Clomipramine Maprotiline Fluoxetine Nefazodone Duloxetine
(1957) Nortriptyline Amoxapine Sertraline
Mirtazapine Agomelatine
Amitriptyline Paroxetine
Desipramine Fluvoxamine Venlafaxine
Citalopram
Phenelzine
Isocarboxazid Bupropion
Tranylcypromine Tianeptine
 Depresion - psychopharmacological treatment
FIRST GENERATION
• (imipramine, clomipramine (Anafranil), amitriptyline, doxepine, nortriptyline, maprotiline,
mianserine)
• anticholinergic effects (urinary retention, constipation, increased intraocular pressure, production
and increased cognitive deficiency);
• antihistaminergic effects (sedation, weight gain);
• side effects of α-NA receptor blockade (sedation, orthostatic hypotension);
• cardiotoxic effects (Q-T interval prolongation, atrio-ventricular block, membrane saturation with ST
segment elevation, arrhythmias, sudden death);
• neurotoxic effects (confusional states, delirium, disordered movements, convulsions);
• special side effects, the risk of death at over-dose, having a very low therapeutic index;
• hypomaniacal or maniacal switch.

THE SECOND GENERATION

SSRI (fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram).
• digestive (nausea, vomiting) due to serotonergic activation of presynaptic 5-HT3 receptors;
• psychomotor agitation and significant increase in anxiety in non-serotonin depressions;
• sedation, dizziness (10-20%), sexual dysfunction in men and women;
• discontinuation syndrome;
• serotonin syndrome;
• extrapyramidal phenomena in vulnerable persons;
 Depresion - psychopharmacological treatment
SSRI
(Selective serotonin reuptake inhibitors)

Fluoxetine: PROZAC, FLUOXIN, MAGRILAN (CP 20MG)

Fluvoxamine: FEVARIN, DEPRIVOX (CP 50, 100 MAG)
Paroxetine: ARKETIS, PALUXETIL, PAXETIN, SEROXAT (CP. 20, 40 MG)
Sertraline: ADJUVIN, SERLIFT, ZOLOFT, SETALOFT, STIMULOTON (CP 50, 100)
Citalopram: LINISAN (CP 20 MG)
Escitalopram: CIPRALEX, DEPRESINAL, ELICEA, ESCITASAN, ESTAN, ESLOREX, LINUXIN,
SERODEPS (CP 10MG)

Possible adverse effects

• digestive (nausea, vomiting) due to serotonergic activation of presynaptic 5-HT3 receptors;
• psychomotor agitation and significant increase in anxiety in non-serotonin depressions;
• sedation, dizziness (10-20%), sexual dysfunction in men and women;
• discontinuation syndrome;
• serotonin syndrome;
• extrapyramidal phenomena in vulnerable persons;
• metabolic syndrome
• Seizures.
 Depresion - psychopharmacological treatment
OTHER ANTIDEPRESSIVE CLASSES

Serotonin, noradrenaline reuptake inhibitors - SNRIs (venlafaxine, duloxetine)

Venlafaxine - ALVENTA, EFECTIN, ELIFY, FOBILESS, IVRYX, VELAXIN, ARGOFAN CPS 37.5 / 75/150
Duloxetine - CYMBALTA, DOZZEX, DULSEVIA, ONELAR, ZATINEX - CPS 30, 60

- effect on pain and anxiety

- effects on chronic myofascial pain, fibromyalgia (duloxetine)
- common adverse effects: nausea, fatigue, constipation, xerostomia. High doses - lead to high blood
pressure

Dopamine reuptake inhibitors - (bupropion) (ZYBAN, ELONTRIL)

Side effects: enhances the proconvulsant risk; rare digestive disorders;
Insomnia, constipation, foggy vision. Indication in addiction to smoking

Other antidepressants used:

Mirtazapine (MIRZATEN, PHARMATAZ, REMERON, ZULIN) - sedative, increases appetite, adverse
effects in glaucoma and urinary retention
Trazodone (TRITTICO) (rec. 5HT2 antagonist) - hypnomodulator, good metabolic profile, can cause hTA
to very rarely priapism.

Antidepressants with serotoninergic modulating action (tianeptin, COAXIL, NOBIXAL) and

serotoninergic / melatoninic (agomelatine) (VALDOXAN)
 Depresion - psychopharmacological treatment
Other

Antipsychotics - Quetiapine IR and XR; olanzapine; Aripiprazole.

Quetiapine XR - adjuvant in recurrent depression

Timostabilizers - Lamotrigine, Valproat (Convulex, Orfiril, Depakine),

Carbamazepine
anxiolytics
thyroid hormones
electroconvulsive therapy
Depresion - nonpsychopharmacological treatment

- cognitive therapy
- behavioral therapy - is based on learning theory (classical and operant conditioning)
- interpersonal therapy
- psychoanalytically oriented psychotherapy
-Supportive psychotherapy
- group therapy
- family therapy
 Depression – special therapeutic strategies
• MAINTENANCE OF TREATMENT
• In the case of liability, maintaining the treatment with the antidepressant chosen for a minimum period of 9 months.
Timostabilizers will be associated with patients who are expected to have a potential risk of hypomaniac turn.
• The appearance of insomnia and anxious anxiety requires the eventual change of the antidepressant.
• The doses used will be gradually reduced, avoiding the discontinuation syndrome.

• TREATMENT OF THE RECURRENT EPISODE

• • it will be avoided to resume treatment with tricyclic or tetracyclic antidepressants;
• • use of the antidepressant given in the first episode in high doses or switching to another antidepressant with
close pharmacological action;
• • the change due to the phenomenon of synaptic dysplasticization from an antidepressant with presynaptic action
to one of the new generation, with dual action;
• • in the case of a favorable response, the treatment will be maintained for at least 12/24 months.

• TREATMENT OF MULTIPLE DEPRESSIVE EPISODES

• The phenomenon of synaptic plasticity indicates the use of second-generation antidepressants, with bimodal or
multiple action, in combination with atypical timostabilizers and / or antipsychotics (olanzapine, quetiapine,
amisulprid in minimal doses) under the conditions of the association of psychotic elements.

• TREATMENT OF RESISTANT DEPRESSION

• • reconsideration of the diagnosis;
• • reconsideration of psychopharmacological matching criteria;
• • reassessment of brain and somatic status;
• • use of "heroic therapies" schemes by combining two new generation antidepressants with different
psychopharmacological mechanisms (SSRI + mirtazapine; venlafaxine + mirtazapine; reboxetine + mirtazapine /
venlafaxine).
 Depression - Evolution and prognosis
• The minimum natural duration of a depressive episode is evaluated at 3-9 months. We recognize:
• • unique depressive episode;
• • 1-3 depressive episodes throughout life;
• • multiple episodes;
• • depressive episodes within the type I, II and III bipolar disorder. In this context, we notice the
tendency of dispositional hypomaniacal or maniacal type turning under antidepressant medication,
especially tricyclic antidepressants and antidepressants of the new generation, with dual action
(type IV bipolar disorder).
• In the evolution of the depressive episode under treatment, the following phases are recognized:
acute, therapeutic response, remission, relapse and recurrence.
• The prognosis is moderate:
• - 15% is remitted
• - 50-60% is partially remitted (multiple relapses with good interrepisodic functioning)
• - At one third some signs of chronic symptomatology and social deterioration persist
• - During the evolution of the depressive episode under treatment, the following phases are
recognized: acute, therapeutic response, remission, relapse and recurrence.

• COMPLICATIONS:
• - the possibility of an increased suicide risk relapse;
• - the turn towards a manic phase under pharmacological treatment;
• -suicide
 Bibliography
• www.psychiatry.org
• www.nimh.nih.gov
 Content:
• Depression – definition
• Depression - Epidemiological Data
• Depression – symptoms
• Depression – clinical interview
• Depression – diagnosis
• Depression – special therapeutic strategies
• Depression - Evolution and prognosis