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Dr David Straton

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SSRIs Brands Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline Cipramil, Celapram, Talam, Talohexal Lexapro, Esipram Prozac, Auscap, Fluohexal, Lovan, Zactin Luvox, Faverin, Movox Aropax, Oxetine, Paxtine Zoloft, Concorz, Eleva, Setrona, Xydep

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SNRIs Brands Desvenlafaxine Duloxetine Venlafaxine Pristiq Cymbalta Efexor Others Bupropion (NDRI) Buspirone (Piperazine) Mianserin (Tetracyclic) Mirtazapine (NaSSA) Moclobemide (RIMA) Reboxetine (NRI) Tranylcypromine (MAOI) Zyban Buspar Tolvon, Lumin Avanza, Axit 30, Mirtazon, Remeron Aurorix, Arima, Clobemix, Maosig, Mohexal Edronax Parnate

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Normal Synapse

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Serotonin

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Synapse in depression

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SSRI increases serotonin 5HT1a

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Some receptors may upregulate

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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 FOI on FDA, all clinical trials, both published and unpublished.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

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Sexual Side-effects TotalDesireArousalOrgasm SevereSertraline27Citalopram55Citalopram82Clomipramine42 Venlafaxine25Paroxetine47Venlafaxine54Paroxetine18 Citalopram20Fluoxetine46Paroxetine44Venlafaxine16 Paroxetine17Sertraline43Sertraline39Sertraline15 Fluoxetine16Venlafaxine23Fluoxetine31Citalopram14 MildDuloxetine4Fluvoxamine6Duloxetine11Fluoxetine12 Escitalopram3Mirtazapine6Fluvoxamine7Mirtazapine4 Fluvoxamine3Duloxetine5Mirtazapine4Escitalopram4 Mirtazapine2Moclobemide4 2Fluvoxamine3 NilPlacebo1Escitalopram1Placebo1 1 Moclobemide0.2Placebo1Escitalopram0.7Moclobemide0.4 Serretti

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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