PRESENTED BY:

NUTHAN

DEPRESSION

INTRODUCTION:

• DEFINITION:

Depression is a common mental disorder characterised

by depressed mood, loss of interest or pleasure,

decreased energy, feelings of guilt or low self-worth,

disturbed sleep or appetite, and poor concentration.

• Depression often comes with symptoms of anxiety. At

its worst, depression can lead to suicide.

EPIDEMIOLOGY:

• Almost 1 million lives are lost yearly due to

suicide, which translates to 3000 suicide deaths

every day (WHO, 2012).

• Depression is the leading cause of disability for

both males and females, the burden of depression

is 50% higher for females than males (WHO,

2008).

• Depression is the leading cause of disease

burden for women in both high-income and low-

and middle-income countries

ETIOLOGY: Depression doesn’t have a single cause.

Brain chemistry, hormones, genetics and personal risk factors may all play a

role.

Risk factors for depression include:

• Low self-esteem

• Anxiety disorder,

• Borderline personality disorder,

• Post-traumatic stress disorder (PTSD)

• Physical or sexual abuse

• Chronic diseases like diabetes, multiple sclerosis,

or cancer

• Alcohol or drug abuse

• Certain prescription medications

• Family history of depression

• Depressive episode involves symptoms such as: depressed

mood, loss of interest and enjoyment, and increased

fatigability.

• Depending on the number and severity of symptoms, a

depressive episode can be categorized as mild, moderate,

or severe.

• An individual with a mild depressive episode will have some

difficulty in continuing with ordinary work and social activities,

but will probably not cease to function completely.

• During a severe depressive episode, on the other hand, it is

very unlikely that the sufferer will be able to continue with

social, work, or domestic activities, except to a very limited

extent.

PATHOPHYSIOLOGY:

SYMPTOMS OF DEPRESSION:

Depression symptoms can vary from mild to severe and can include:

• Feeling sad or having a depressed mood.

• Loss of interest or pleasure in activities once enjoyed.

• Changes in appetite — weight loss or gain unrelated to dieting.

• Trouble sleeping or sleeping too much.

• Loss of energy or increased fatigue.

• Increase in purposeless physical activity (e.g., hand-wringing or pacing) or slowed movements and speech (actions observable by others)

• Feeling worthless or guilty.

• Difficulty thinking, concentrating or making decisions.

• Thoughts of death or suicide.

MANAGEMENT:

• The main stay of treatment is Anti- Depressants

although, psychological treatment have found as

an alternative to antidepressants ( for milder

forms of depression).

• Other methods of treating depression – vagus

nerve stimulation, transcranial magnetic

stimulation ( not widely used).

CHOICE OF DRUG:

NICE guidance: treatment for depression

• Antidepressants aren’t recommended as 1st line treatment in

recent-onset, mild depression.

• Antidepressants recommended for treatment of moderate to

severe depression and for dysthymia.

• SSRI is recommended with antidepressant.

• All patients should be informed about the withdrawal effects of

antidepressants.

• For treatment resistant depression, lithium or an

antipsychotic or addition of second antidepressant.

• Patient with 2 prior episodes and functional impairment should

be treated for 2 years.

• Use of ECT in severe and treatment resistant depression is

recommended.

Antidepressants effectiveness:

• The severity of depression at which antidepressants

show consistent benefits over placebo is poorly

defined.

• The more severe the symptoms the greater the

benefit.

• In patients with subsyndromal depression, it is difficult

to separate the response rate to antidepressants from

that to placebo; antidepressant treatment is not

indicated unless the patient has a history of severe

depression or if symptoms persist.

Onset of action:

• Antidepressants do not exert their effects for 2-4

weeks. This is a myth. All the antidepressants

show a pattern of response where the

improvement rate is highest during 1-2 weeks and

lowest during 4-6.

• In clinical practice an antidepressant effect in an

individual is usually seen by 2 weeks. It follows

that in individuals in whom no anti depressant

effect is evident after 3-4 weeks treatment, a

change in dose or drug is indicated.

Choice of antidepressants and

relative side effects:

• SSRI’s are well tolerated compared with the older

TCA’s and MAOI’s and are generally recommended

as first line pharmacological treatment for depression.

• There is a suggestion that some antidepressants may

be effective overall than others and therefore be

treated with caution.

• Side effect profiles of antidepressants do differ: EX:

Paroxetine has been associated with more weight gain

and higher incidence of sexual dysfunction

Sertraline with higher incidence of diarrhoea than other

SSRI’s.

Cont.…

• New dual reuptake inhibitors such as venlafaxine and

duloxetine tend to tolerate well than SSRI’s but better than

TCA’s.

• As well as headache and GI symptoms, SSRI’s as a class are

associated with a range of other side effects, including sexual

dysfunction, hyponatremia, and GI bleeds.

• TCA’s have a number of adverse cardiovascular effects –

hypotension, tachycardia, QTc prolongation and particularly

toxic in over dose.

• MAOI’s have potential to interact with tyramine- containing

foods(cheddar, tofu, bean curd, fish such as salami, sausage,

smoked meat,) causing hypertension.

Drug interactions:

• SSRI’s are potent inhibitors of individual or multiple

hepatic cytochrome P450 pathways and magnitude of

these effects is dose related.

EX: Fluoxetine is potent CYP2D6 inhibitor result in

increased seizures risk with clozapine.

Fluvoxamine is potent CYP1A2 inhibitor result in

increased theophylline serum levels.

Paroxetine is potent CYP2D6 inhibitor result in

treatment failure with tamoxifen leading to increased

mortality.

• Pharmacodynamic interactions:

Cardiotoxicity of TCA’s exacerbated by drugs such as

diuretics causing electrolyte disturbances.

Suicidality:

• . Antidepressant treatment has been associated with an

increased risk of suicidal thoughts and acts particularly in

adolescents and young adults.

• Patients should be warned of this potential side effect

during early weeks of treatment.

• The most effective way to prevent suicidal thoughts and

act is to treat depression and antidepressant drugs are

the most effective treatment available.

Duration of the treatment:

• Antidepressants relieve the symptoms of depression but

don’t treat the underlying cause.

• They should be taken for 6-9 months after recovery from

a single episode.

• In patients with multiple episodes, there is evidence of

benefit from maintenance treatment for at least 2 years.

Next step treatments:

• Approximately 1/3rd of patients do not respond to the

first antidepressants that is prescribed.

• Options in this group include dose escalation,

switching to different drug.

• Sequenced Treatment Alternatives to Relieve

Depression (STAR-D) programme states that a

small proportion of non-responders will respond with

each treatment change, but the effect sizes are

modest and there is no clear difference in

effectiveness between strategies.

Antidepressant prophylaxis:

• First Episode: A single episode of depression should be treated

for at least 6-9 months after full remission.

If antidepressant therapy is stopped immediately

on recovery, 50% of patients experience a return

of their depressive symptoms within 3-6 months.

Non- continuous use of antidepressants during

first 6 months of treatment predicts higher rates

of relapse.

Antidepressant prophylaxis:

• Recurrent Depression: 50-80% will go on to have

a second episode, and 80-90% of those have a second

episode will go on have a third.

• Factors to increase risk of recurrence: Family history of

depression, recurrent dysthymia(persistent mild

depression), non affective psychiatric illness, female

gender, degree of treatment resistance, chronic medical

illness and social factors.

• People with depression are at increased risk of CVD.

• Risk of relapse is greatest in the first few months after

discontinuation.

Summary of NICE guidance: recommendation regarding antidepressant prophylaxis

• Patient who have 2 or more episodes of depression in

the recent past, and who have experienced significant

functional impairment should be advised to continue

antidepressants for atleast 2 years.• Patients on maintenance treatment should be re-

evaluated by age, co-morbid conditions, and other risk

factors in decision to continue maintenance treatment

beyond 2 years.

[NICE : National Institute for Health and Care Excellence]

Dose for prophylaxis:

• Adults should receive same dose as used for acute

treatment.

• In elderly patients use of lower doses: dosuelpin

75mg/day offers effective prophylaxis.

• Relapse rates after ECT are similar to those after

stopping antidepressants.

• Lithium has some efficacy in the prophylaxis of unipolar

depression. NICE recommends lithium shouldn’t be used

as the sole prophylactic drug. There is supportive

evidence for use of combination with nortriptyline.

• Maintenance treatment with lithium prevents suicide.

Treatment for resistant depression:

or combination

Treatment for resistant depression:• First choice:

Treatment of psychotic depression:

• Psychotic symptoms can occur across the whole

spectrum of depression severity.

• Combined treatment with antidepressant and

antipsychotic is often recommended as first line therapy.

• TCA’s are probably more effective than newer

antidepressants in the treatment of psychotic

depression.

• In clinical practice only a small proportion of patients with

psychotic depression receive an antipsychotic drug,

perhaps reflecting clinicians uncertainty regarding

risk/benefit ratio of this treatment strategy.

Treatment of psychotic depression:

• Antipsychotic drugs such as quetiapine and olanzapine

have useful antidepressant effects as well as

antipsychotic and so there is empirical basis for their use

as additive agents to antidepressant treatment.

• Psychotic depression is one of the indications for ECT.

• ECT is more protective against relapse in psychotic

depression than in non-psychotic depression.

• There is no specific indication for other therapies or

augmentation/combination strategies in psychotic

depression.

Treatment of psychotic depression:

• Overview:• TCA’s are probably first choice in psychotic depression.

• SSRI’s/SNRI’s (serotonin and noradrenaline reuptake

inhibitors) are 2nd line alternative when TCA’s are poorly

tolerated.

• Augmentation of an antidepressant with Olanzapine or

Quetiapine has a reasonable empirical basis.

• ECT should always be considered where a rapid

response is required or whether treatments have failed.

REFERNCES:

• http://www.who.int/mental_health/manageme

nt/depression/who_paper_depression_wfmh

_2012.pdf

• Maudsley prescribing guidelines in

psychiatry[ 11th edition]