depression & antidepressants

1. PRESENTED BY:
NUTHAN
DEPRESSION

2. 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.

3. 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

4. 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

5. • 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.

6. PATHOPHYSIOLOGY:

7. 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.

8. 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).

9. CHOICE OF DRUG:

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

30. 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.

31. 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.

32. 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.

33. 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.

35. 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.

36. 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.

37. 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]

38. 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.

39. Treatment for resistant depression:
or combination

40. Treatment for resistant depression:
• First choice:

46. 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.

47. 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.

48. 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.

49. REFERNCES:
• http://www.who.int/mental_health/manageme
nt/depression/who_paper_depression_wfmh
_2012.pdf
• Maudsley prescribing guidelines in
psychiatry[ 11th edition]