SSRI effects 5HT1a Anxiety down, mood up 5HT2a Insomnia, sex
problems 5HT2c Agitation 5HT3 Nausea
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Major studies and meta-analyses 2008-9 STAR*D (Sequenced
Treatment Alternatives to Relieve Depression). 26th Feb 2008, PLoS
Medicine published the Hull meta-analysis of anti- depressant
trials from the FDA. 18th Nov 2008, the American College of
Physicians published two background papers on anti-depressants.
28th Jan 2009, the Lancet published online a major meta-analysis of
antidepressants. 3rd Feb 2009, the Canadian Medical Association
Journal published a review of studies about whether SSRIs increase
the risk of suicide. June 2009, the Journal of Clinical
Psychopharmacology published a meta-analysis of anti-depressant
related sexual dysfunction. In August 2009, the BMJ published a
meta-analysis on suicidality.
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STAR*D (Sequenced Treatment Alternatives to Relieve
Depression)
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The Hull meta-analysis Attempt to avoid publication bias. FOI
on FDA, all clinical trials, both published and unpublished. Trials
with no benefit + no data left out. (Citalopram and sertraline).
Most trials only 6 weeks duration. Conclusion, drug only beat
placebo in most severe depressions.
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Hull
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The American College of Physicians Reviews Overall, no
substantial differences in efficacy Fluvoxamine lost every
comparison test for efficacy Venlafaxine prone to nausea Sertraline
prone to diarrhoea Mirtazapine prone to weight gain Venlafaxine and
paroxetine prone to discontinuation syndrome
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Fluvoxamine compared to other anti-depressants ACP
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Fluvoxamine compared to other anti-depressants
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I.e Fluvoxamine lost every drug-to-drug contest ACP Fluvoxamine
compared to other anti-depressants
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Lancet meta-analysis
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Odds of being most effective 1) Mirtazapine24.4% 2)
Escitalopram23.7% 3) Venlafaxine22.3% 4) Sertraline20.3% 5)
Citalopram3.4% 6) Milnacipran2.7% 7) Bupropion2.0% 8)
Duloxetine0.9% 9) Fluvoxamine0.7% 10) Paroxetine0.1% 11)
Fluoxetine0.0% 12) Reboxetine0.0% Lancet
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Odds of being most acceptable 1) Escitalopram27.6% 2)
Sertraline21.3% 3) Bupropion19.3% 4) Citalopram18.7% 5)
Milnacipran7.1% 6) Mirtazapine4.4% 7) Fluoxetine3.4% 8)
Venlafaxine0.9% 9) Duloxetine0.7% 10) Fluvoxamine0.4% 11)
Paroxetine0.2% 12) Reboxetine0.1% Lancet
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Suicide Risk (CMAJ) CMAJ
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Copyright 2009 BMJ Publishing Group Ltd. Odds of suicidality
(ideation or worse) for active drug relative to placebo by age in
adults Stone, M. et al. BMJ 2009
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Suicide risk (BMJ) Suicidality risk vs placebo (ideation or
worse) in adults Drugn%Placebon%Odds ratio
Escitalopram1031300.32%526040.19%2.44
Citalopram2426610.90%713710.51%2.11
Fluvoxamine2221871.01%1318280.71%1.25
Mirtazapine810160.79%66440.93%0.97
Paroxetine5099190.50%2969720.42%0.93
Duloxetine2523271.07%1814601.23%0.88
Venlafaxine2955930.52%3039040.77%0.71
Fluoxetine8171801.13%6748141.39%0.71
Sertraline1863630.28%2850810.55%0.51 All
drugs314500430.63%197271640.73%0.83 BMJ
S-(+)-citalopram (Escitalopram)R-(-)-citalopram 50/50 mixture
of both = Citalopram
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Treatment algorithm: plan A Escitalopram. 2.5mg rising to 20
mg. Similar to Level 1 in STAR*D 2 nd for efficacy in Lancet
meta-analysis 1 st for acceptability in Lancet meta-analysis Mild
sex side-effects Trial should last at least 2 months. Possible
disadvantage if suicide risk high (BMJ)
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Treatment algorithm: plan B (in no particular order) Add
thyroxine, esp if T4
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Treatment algorithm: plan C California rocket-fuel Combination
of: Venlafaxine 75 300 mg Mirtazapine 30 60 mg
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Treatments to abandon Fluvoxamine Reboxetine Augmentation with
lithium for unipolar depression
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Treatments to downplay Paroxetine Antidepressants in
adolescents, especially venlafaxine and paroxetine
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Treatments in danger of being abandoned prematurely
Tranylcypromine. 'Approximately 30% of participants in the
tranylcypromine group had less than 2 weeks of treatment, and
nearly half had less than 6 weeks of treatment (STAR*D)
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Papers mentioned available here:
psyberspace.com.au/depression