Antidepressants

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Antidepressants

• M. Awais Riaz

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How well do they work?

• After 3 months of treatment, the proportions of
  people with depression who will be much improved
  are
• 50 and 65 if given an antidepressantcompared
  with25 - 30 if given a placebo
• Refhttp//www.rcpsych.ac.uk/mentalhealthinformati
  on/mentalhealthproblems/depression/antidepressants
  .aspx

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St Johns Wort

• Popular unlicensed remedy
• Should be asked for before initiating treatment
• ADs should not be used with it

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Management

• Review 1-2 weeks at start
• Rx should be continued for at least 4 weeks (6
  weeks in elderly) before stopping
• Following remission treatment should continue for
  4-6 months (12 months in elderly)
• Recurrent depression should be treated for at
  least 5 years, may be indefinitely

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Failure to respond

• Failure to respond to an initial AD may
  necessitate an increase in dose or switch class
• Failure to respond to a 2nd drug may require
  addition of lithium, ECT or psychotherapy

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ADs and Hyponatraemia

• Usually due to inappropriate secretion of ADH
• More frequently with SSRI
• CSM advise is to consider it in all patients who
  develop drowsiness, confusion or convulsions on
  treatment with ADs

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TCA

• 2 main classes , Sedatives and less- sedatives
• Agitated anxious patients respond best to
  sedatives
• Withdrawn apathetic benefit from less sedating
  ones

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TCA - caution

• Not to be used in children with depression
• Cardiac arrhythmias
• Anti muscarinic SEs
• Dangerous in ODs

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MAOIs

• Less frequently used due to many side effects and
  dietary interactions
• Used for atypical depression and phobic patients
• No other AD should be prescribed within 2 weeks
  of stopping or starting MAOIs

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SSRIs

• Better tolerated than TCA MAOI
• Less sedating, have fewer anti muscarinic and
  cardiotoxic effects

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Other AD - Duloxetine

• Used for major depressive disorder, diabetic
  neuropathy and stress incontinence

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Other AD - Flupentixol

• Depressive illness with psychoses
• Caution in heart , liver, kidney and parkinsons
  disease
• SE insomnia , restlessness, EPS

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Other AD - Mirtazapine

• Major depression
• Fewer anti muscarinic SEs but causes sedation
• Cautions Cardiac problems, DM , psychoses

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Other AD - Venlafaxine

• Used for major depression and generalised anxiety
  disorder
• Can cause Cardiac arrhythmia

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Recognised Minimum effective doses (mg/day)

• Tricyclics Unclear at least 75-100, possibly 125
• Others
• Mirtazapine 30
• Venlafaxine 75
• SSRI
• Citalopram 20
• Fluoxetine 20
• Paroxetine 20
• Sertaline 50

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NICE and ADs a summary

• AD are not recommended in mild depression
  watchful waiting, problem-solving and exercise
  more effective.
• When an AD is prescribed , a generic SSRI
  recommended
• All patients should be informed about withdrawal
  effects of AD
• For severe or resistant depression a combination
  of AD and CBT recommended
• Patients with 2 prior episodes and functional
  impairment should be treated for at least 2 years

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MHRA/CSM Expert working group on SSRIs a summary

• Use the lowest possible dose
• Monitor closely in early stages for restlessness,
  agitation and suicidality, this is particularly
  important in young people (lt30 yrs)
• Doses should be tapered gradually on stopping
• Venlafaxine is CI in uncontrolled HTN. Avoid in
  Heart Disease. Regular BP monitoring is
  recommended

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AD and suicide risk
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ADs and suicide risk

• BMJ 2007334215
• Current use of any AD in a suicidal patient is
  associated with an increased risk of attempted
  suicide, and an overall decreased risk of
  completed suicide and death
• Latest research suggest that venlafaxine has a
  slightly higher level of suicide risk compared to
  other AD it should not be used first line ( as
  per NICE guidelines)

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ADs and suicide risk

• BMJ 2005330373
• Current evidence shows that SSRIs are effective
  in moderate and severe depression and that there
  is NO relation with completed suicide
• But, we should be aware that all ADs may induce
  or worsen suicidal ideation during the early
  phase of treatment

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MHRA update May 2006

• Trial data show increased risks associated with
  the use of venlafaxine and most SSRIs
  antidepressants in children. Clinical trials in
  adults have not been powered to detect changes in
  suicidal behaviour, and it is not possible to
  rule-out an increased risk in some susceptible
  individuals. Given the identified risk in
  children/adolescents, it is probable that some
  increased risk remains present in young adults,
  and the venlafaxine clinical trial data are
  tentatively suggestive of a possible increased
  risk in the 18-29 year age-group. Although this
  issue relates to therapeutic treatment, rather
  than overdose toxicity, any differences between
  drugs may result in differences in observed
  fatality rates.

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CSM advice for under 18s

• Only fluoexetine has been shown in clinical
  trials to be effective for treating depressive
  illness in children and adolescents. However it
  is possible that , in common with other SSRIs, it
  is associated with a small risk of self harm and
  suicidal thoughts. Overall the balance of risks
  and benefits for fluoxetine in lt 18 is considered
  favourable , but they should be carefully
  monitored for suicidal behaviour, self harm or
  hostility , particularly at the beginning of
  treatment.

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References

• BNF
• NICE Guidelines
• The Maudsley Prescribing Guidelines
• BMJ
• MHRA