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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by TriedEveryMedication on April 17, 2011, at 23:04:10
The Viibryd PI is out.
(http://www.frx.com/pi/viibryd_pi.pdf)
Was looking at the efficacy. Seems to be 2.5 to 3.2 points more reduction in depression after 8 weeks than the placebo (MADRS scale).Lexapro seems to be about 5 or 6 MADRS clicks lower than placebo after 8 weeks from what I have read.
That does not sound too good. I had some hopes for this newest iDrug and was getting ready to camp out in front of walgreens on launch day.
Maybe not :D
Here's the info on the sides, vs. placebo:
.................VIIBRYD(436).....Placebo(433)
Gastrointestinal disorders
Diarrhea.............28.............9
Nausea...............23.............5
Dry mouth.............8.............5
Vomiting..............5.............1
Dyspepsia.............3.............2
Flatulence............3.............2
Gastroenteritis.......3............<1
Nervous system disorders
Dizziness.............9.............5
Somnolence............3.............2
Paresthesia...........3.............1
Tremor................2.............0
Psychiatric disorders
Insomnia..............6.............2
Abnormal dreams.......4.............1
Libido decreased......4............<1
Restlessness *........3............<1
Orgasm abnormal.......3.............0
General disorders
Fatigue...............4.............3
Feeling jittery.......2............<1
Cardiac disorders
Palpitations..........2............<1
Musculoskeletal and connective tissue disorders
Arthralgia............3.............2
Reproductive system and breast disorders
Delayed ejaculation...2.............0
Erectile dysfunction..2.............1
Metabolism and nutrition disorders
Increased appetite....2.............1
Posted by SLS on April 18, 2011, at 5:57:52
In reply to Viibryd/Vilazodone PI and efficacy..., posted by TriedEveryMedication on April 17, 2011, at 23:04:10
It may be that this drug will act as an augmenter of other antidepressants to treat depression. It should also reduce anxiety.
- Scott
Posted by SLS on April 18, 2011, at 6:02:43
In reply to Re: Viibryd/Vilazodone PI and efficacy..., posted by SLS on April 18, 2011, at 5:57:52
If you skip over vilazodone, you will no longer hold the distinction of having tried every drug. However, you are exercising good judgment in being cautious. If not vilazodone, I hope you find an acceptable treatment.
My hope has lied in the possibilities of drug combinations, even though I had tried every drug.
- Scott
Posted by mtdewcmu on April 22, 2011, at 19:04:23
In reply to Re: Viibryd/Vilazodone PI and efficacy... » SLS, posted by SLS on April 18, 2011, at 6:02:43
>
> My hope has lied in the possibilities of drug combinations, even though I had tried every drug.
>Some pharma company should come out with a pill that is a mixture of every other AD on the market. How could that fail?
Posted by bearfan on April 25, 2011, at 16:47:01
In reply to Viibryd/Vilazodone PI and efficacy..., posted by TriedEveryMedication on April 17, 2011, at 23:04:10
If the sexual side effects and weight gain are truly less, I'd take slightly less efficacy for a pill that doesn't cause those side effects. There was a video of a Doctor that had experience with it, he stated that it worked much like existing drugs without those side effects.
Posted by SLS on April 26, 2011, at 5:53:57
In reply to Re: Viibryd/Vilazodone PI and efficacy..., posted by bearfan on April 25, 2011, at 16:47:01
> If the sexual side effects and weight gain are truly less, I'd take slightly less efficacy for a pill that doesn't cause those side effects. There was a video of a Doctor that had experience with it, he stated that it worked much like existing drugs without those side effects.
"Less efficacy" can mean that fewer people respond to Viibryd statistically. However, it doesn't always reflect the magnitude of the improvement that occurs when there is a response. If Viibryd works for fewer people, perhaps for those whom do respond to it, it might very well bring those people to full remission.
Viibryd is a serotonin reuptake inhibitor with the additional property of 5-HT1a agonism. This property should help reduce excessive serotonergic activity that would otherwise produce sexual side effects. In this regard, Viibryd is somewhat like Buspar, a drug sometime chosen to remedy SRI-induced sexual side effects.
Here's a nice review of the treatment of SRI-induced sexual dysfunction.
http://www.medscape.com/viewarticle/430614_5
Treatment of Antidepressant-Induced Sexual Dysfunction: Treatment of Sexual Side Effects: Antidotes
Authors and Disclosures
Print This Print This
Abstract & Introduction
Differential Diagnosis of Sexual Dysfunction
Antidepressants and Sexual Dysfunction
Treatment of Sexual Side Effects: General Strategies
Treatment of Sexual Side Effects: Antidotes
SummaryReferences
Information from Industry
For your patients with advanced prostate cancer
A novel FDA-approved treatment option
Learn more
Treatment of Sexual Side Effects: AntidotesA variety of antidotes have been reported to treat SSRI-induced sexual dysfunction effectively; however, virtually all the data on these agents are derived from open case reports and case series. Insofar as sexual function improvement may be responsive to placebo effects, it is impossible to estimate the true efficacy of these antidotes.[27]
Most of these antidotes either have serotonin-blocking properties (especially 5HT-2 antagonistic effects) or augment catecholamine activity, especially that of dopamine. The antiserotonergic antidotes are cyproheptadine, buspirone, nefazodone, and mianserin. Medications enhancing dopaminergic tone include amantadine, bupropion, and stimulants, with yohimbine showing noradrenergic effects. Among the reported antidotes, the only 2 without antiserotonergic effects or catecholaminergic activity are gingko biloba and urecholine.
Cyproheptadine is an antihistamine with antiserotonergic properties that has been reported for over a decade to reverse antidepressant-induced sexual dysfunction. Only case reports and case series attest to its efficacy.[13,42-44] Effective doses range from 2mg to 16mg. In the most recent and largest case series, 12 of 25 patients described improvement in sexual function when treated with cyproheptadine (mean dose, 8.6mg).[13] Anorgasmia is the sexual side effect most often reported to be alleviated by cyproheptadine. Cyproheptadine is effective when taken either on an as-needed basis (typically, 1 to 2 hours before intercourse) or on a regular basis.
However, cyproheptadine's utility is often limited by its potential side effects. Excessive sedation and the reversal of the therapeutic effect of the antidepressant are major problems that limit its usefulness. Effectively treated depression and bulimic symptoms have been reported to reemerge soon after cyproheptadine was started.[42,45-48] This reversal of therapeutic effects is itself reversible upon discontinuation.
Buspirone is a serotonin-IA partial agonist typically prescribed to treat persistent anxiety. One case series reported that buspirone reversed both decreased sexual interest and orgasmic dysfunction caused by SSRIs.[49] Most patients using buspirone to treat sexual dysfunction take it daily. The dosage is the same as that used for anxiety (15mg to 60mg daily). The mechanism of action of buspirone in treating sexual dysfunction may be reduction of serotonergic tone via stimulation of presynaptic autoreceptors or the alpha-2 antagonist effects of one of buspirone's major metabolites, 1-pyrimidinylpiperazine.
Nefazodone and mianserin are antidepressants with strong postsynaptic blocking properties. In one case report, nefazodone 150mg taken 1 hour prior to sexual activity completely reversed sertraline-induced anorgasmia.[50] Mianserin, an antidepressant with 5HT-2 and alpha-2 adrenergic antagonist properties, is available in many countries but not in the US. It has been reported to reverse serotonin reuptake inhibitor-induced sexual dysfunction in 9 of 15 patients.[51] Mirtazapine is similar in its biological activity to mianserin and might also be effective in reversing sexual side effects. No case reports or case series have yet been published attesting to this, although clinicians have described such an effect. The putative capacity of mianserin and mirtazapine to reverse sexual side effects can be attributed either to their serotonergic activity or presynaptic alpha-2 activity.
Amantadine, a dopamine agonist, is used both as an antiviral agent and as a treatment for Parkinson's disease. It has been shown in a number of small case series to reverse anorgasmia.[13,52-54] Reported effective doses have ranged between 100mg to 400mg taken either on a daily or as-needed basis. In the most recent case series, 8 (42%) out of 19 patients with SSRI-induced sexual dysfunction improved with amantadine 200mg daily.[13] Given dopamine's consistent effect as a neurotransmitter involved in sexual arousal, a number of other dopamine agonists have been explored as treatments for sexual side effects.[2,55,56]
Bupropion is another commonly touted antidote for SSRI-induced sexual dysfunction.[57,58] It is assumed that the mechanism of action by which bupropion reverses sexual side effects is its weak dopamine agonism. The evidence for bupropion's efficacy is scant, except for unpublished, anecdotal reports, one case report,[57] and a case series[58] in which 31 (66%) of 47 patients showed improvement when bupropion was added to the regimen along with the serotonergic antidepressant. Most patients (18/31) with a successful outcome responded to as-needed use of bupropion 75mg to 150mg. Libido, arousal, and orgasmic difficulties were all effectively reversed. Fifteen percent of treated patients stopped taking bupropion because of its stimulation side effects. It is unclear whether bupropion doses need to be somewhat lower than usual when added to fluoxetine or paroxetine, to compensate for pharmacokinetic interactions resulting in increased bupropion levels.[59]
Stimulants, such as methylphenidate, D-amphetamine, and pemoline, are reported to reverse a variety of sexual side effects caused by SSRIs or MAOIs.[60-62] Low doses of 10mg-25mg of methylphenidate or D-amphetamine have been effective. One should add stimulants to an MAOI with extreme caution because of the risk of a hypertensive episode. However, use of an MAOI/stimulant combination has been shown to be safe in a case series.[63] SSRI/stimulant combinations show no similar risks.
Yohimbine is available with or without a prescription (and with unclear purity) in health food stores. It is an alkaloid from the bark of Corynanthe yohimbi (family, Rubiaceae) and has been used for decades to reverse erectile dysfunction.[64-66] Its efficacy in treating sexual dysfunction may be associated with its ability to block presynaptic alpha-2 adrenergic sites, leading to enhanced adrenergic tone.[65] A variety of sexual side effects have been reported to be alleviated by yohimbine in doses ranging from 2.7mg to 16.2mg daily, prescribed either on a regular 5.4mg 3 times daily basis or on an as-needed basis with single doses up to 16.2mg.[13,67-69] In the largest case series, 17 (81%) of 21 patients showed improvement of sexual side effects when treated with yohimbine (mean dose, 16.2mg).[12]
Typical side effects associated with yohimbine include anxiety, nausea, flushing, urinary urgency, and sweating. Yohimbine has been the subject of the only double-blind, placebo-controlled study to evaluate treatment of sexual dysfunction occurring as a drug side effect.[27] Unfortunately, the placebo effect was marked, showing a minimal drug-placebo difference with yohimbine given at a dose of 5.4mg 3 times daily. Yohimbine is also available in lower potency without a prescription. The purity, potency, and safety of these preparations, however, are unknown.
Bethanechol is a cholinergic agonist that has occasionally been useful in reversing sexual dysfunction associated with TCAs and MAOIs.[70-73] Typical doses are 10mg to 20mg as needed or 30mg to 100mg daily in a divided dose. Potential side effects with bethanechol include diarrhea, cramps, and diaphoresis. No reports have evaluated or suggested the efficacy of bethanechol for treating SSRI-induced sexual side effects.
Gingko biloba is an herbal extract reported to reverse a variety of sexual dysfunctions associated with antidepressants. Information about gingko's ability in this regard is derived from the experience of 1 clinician presenting a large case series.[74] The response rate was greater than 80%, with doses ranging from 60mg twice daily to 120mg twice daily (mean daily dose, 207mg). Reported side effects include gastrointestinal upset, lightheadedness, and stimulation effects. Because gingko may inhibit platelet-activating factor, caution should be used in considering its use by any patient with a bleeding diathesis. The mechanism by which gingko might alleviate sexual dysfunction is unknown.
- Scott
Posted by mtdewcmu on April 26, 2011, at 12:02:57
In reply to Re: Viibryd/Vilazodone PI and efficacy..., posted by SLS on April 26, 2011, at 5:53:57
I thought that 5-ht1a was the main receptor that you wanted to stimulate in depression. Viibryd is reported to be a partial agonist at 5-ht1a, which would tend to put a ceiling on 5-ht1a effects. However, there should be no ceiling on effects at 5-ht2a, so it might make an interesting psychedelic <g>.
Posted by SLS on April 26, 2011, at 18:44:27
In reply to Re: Viibryd/Vilazodone PI and efficacy..., posted by mtdewcmu on April 26, 2011, at 12:02:57
> I thought that 5-ht1a was the main receptor that you wanted to stimulate in depression. Viibryd is reported to be a partial agonist at 5-ht1a, which would tend to put a ceiling on 5-ht1a effects. However, there should be no ceiling on effects at 5-ht2a, so it might make an interesting psychedelic <g>.
If I remember correctly, the 5-HT1a receptors that Viibryd partially agonizes are somato-dendritic autoreceptors. The greater the stimulation of 5-HTta autoreceptors, the greater the inhibition of serotonin synthesis and release. There are postsynaptic 5-HT1a receptors, too. They are localized in the hippocampus. When these receptors are stimulated, explicit memory function can suffer. Blockade of these receptors can improve explicit memory. Tandospirone, a 5-HT1a agonist, is sometimes used to study these receptors.
I wish there were a "Psychopharmacology For Dummies" book with easy-to-interpret charts to keep track of all of this.
- Scott
Posted by mtdewcmu on April 26, 2011, at 20:58:13
In reply to Re: Viibryd/Vilazodone PI and efficacy... » mtdewcmu, posted by SLS on April 26, 2011, at 18:44:27
> I wish there were a "Psychopharmacology For Dummies" book with easy-to-interpret charts to keep track of all of this.
>Goodman & Gilman's The Pharmacological Basis of Therapeutics is a good book, though not aimed at dummies. I have access to an online version through a previous employer, which luckily hasn't canceled my account. I didn't read the entire chapters on serotonin and antidepressant drugs, as it can get dull. Even there, you might not find the kind of extreme detail you're talking about, though. Complete data on the differences in affinities for subtypes of subtypes of receptors might only be found in research papers (which I can read many of through previous employer as well).
I also found one of Stephen Stahl's books at the public library, but, again, I'm not sure it contained that level of detail.
Posted by SLS on April 27, 2011, at 5:20:54
In reply to Re: Viibryd/Vilazodone PI and efficacy... » SLS, posted by mtdewcmu on April 26, 2011, at 20:58:13
> > I wish there were a "Psychopharmacology For Dummies" book with easy-to-interpret charts to keep track of all of this.
> >
>
> Goodman & Gilman's The Pharmacological Basis of Therapeutics is a good book, though not aimed at dummies. I have access to an online version through a previous employer, which luckily hasn't canceled my account. I didn't read the entire chapters on serotonin and antidepressant drugs, as it can get dull. Even there, you might not find the kind of extreme detail you're talking about, though. Complete data on the differences in affinities for subtypes of subtypes of receptors might only be found in research papers (which I can read many of through previous employer as well).
>
> I also found one of Stephen Stahl's books at the public library, but, again, I'm not sure it contained that level of detail.
>
I like Stephen Stahl because he has the ability to make almost anything understandable.When was Goodman & Gilman's last updated? It has been around for a long time.
Thanks for the suggestions.
- Scott
Posted by mtdewcmu on April 27, 2011, at 11:16:46
In reply to Re: Viibryd/Vilazodone PI and efficacy... » mtdewcmu, posted by SLS on April 27, 2011, at 5:20:54
>
> I like Stephen Stahl because he has the ability to make almost anything understandable.
>Sometimes I wonder if Stephen Stahl isn't just making it up as he goes along. He presents a lot of combinations that sound good from a theoretical standpoint, but where's the data? So I'm sure you can learn some hard information from Stahl, but some of it is more cookbook than text book.
> When was Goodman & Gilman's last updated? It has been around for a long time.
>A quick Amazon search shows that the 12th edition of G&G came out in December. Viibryd is probably still too new. It is pricey, but my public library has a copy of the 10th edition, and any medical school library ought to have it.
Posted by mtdewcmu on April 27, 2011, at 14:03:51
In reply to Re: Viibryd/Vilazodone PI and efficacy... » mtdewcmu, posted by SLS on April 27, 2011, at 5:20:54
Another book I want is Manual of Drug Interaction Principles for Medical Practice by Gary H. Wynn. Drug interactions can make a big difference and this looks like a great book on the subject. You can read some of it on google books.
Posted by TriedEveryMedication on April 27, 2011, at 20:34:03
In reply to Re: Viibryd/Vilazodone PI and efficacy... » mtdewcmu, posted by SLS on April 27, 2011, at 5:20:54
>
> I like Stephen Stahl because he has the ability to make almost anything understandable.
>I don't trust stahl's book. What really goes on in the brain is far more complex than his cutesy diagrams show.
I think this amazon reviewer sums it up well:
=Psychopharmocology easy to do badly and very
=difficult to do well. As a second year psychiatry
=resident in 1999 I thought this book was awesome -
=psych meds made easy, with neat pictures, and
=cool names like "California Rocket Fuel."
=Now that I practice general psychiatry in the
=community I realize that this book is misleading
=and potentially dangerous. One, it oversimplifies
=the neurobiology of psychotropics - although that
=is not all that serious a problem. More importantly,
=it encourages approaching real treatment decisions
=by thinking about neurotransmitters, not the REAL
=source of any actual knowledge we have about how
=these meds work - clinical trials. The result is
=that I have seen many prescribers think about
=tweaking chemical or treating each symptom with
=a different med, frequently leading to expensive
= and often dangerous polypharmacy. For a
=cartoon-like overview for a non prescribing
=practitioner, this is an entertaining but inaccurate
=introduction to psychopharm; for someone who will
=actually use this to guide their prescribing -
=your patients deserve better.
Posted by SLS on April 28, 2011, at 4:43:09
In reply to Re: Stahl » SLS, posted by TriedEveryMedication on April 27, 2011, at 20:34:03
>
> >
> > I like Stephen Stahl because he has the ability to make almost anything understandable.
> >
>
> I don't trust stahl's book. What really goes on in the brain is far more complex than his cutesy diagrams show.I'll take that under advisement.
Thanks.
- Scott
Posted by desolationrower on April 30, 2011, at 3:27:30
In reply to Re: Stahl » TriedEveryMedication, posted by SLS on April 28, 2011, at 4:43:09
I sort of agree, in that while one does know (mostly) what receptors a drug acts upon, you don't know what neutransmitters or circuits are wierd in your head. But, studies obscure quite a lot too. THey have various clinical methodologies, various scales for measuring change, different populations they are recruiting from, etc.
Maybe its just my values, but i think willingness to disregard tradition is useful, and afaict the main way of choosing a drug psychiatrists use is either 'pick one out of a hat' or decide one is 'good' because you noticed a better response rate, damn blinding or placebo.
-d/r
This is the end of the thread.
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