“If you have a drug that makes $4Billion dollars per year, but then are sued/fined for an incredible $3Billion(!); You still have a Billion dollars…plus four per year”
☼COLOR CODED QUICK REF☼| ALL ARE ~DX BY EXCLUSION
*Do initial work up/rule out. Dont alter stable pts Rx.
Hickims dictum [iff LT pt or review rfl] for case; everyone gets a plain film cxr; re-bloods: everyone gets glucose; everyone gets thyroid; some get ekg; conduct own history wo opening pt file. re-check for “reported so recorded” problems or too early abstractions (COPD/Anx-Dep/ADHD etal child beh/BiPD/BPD/EtOH (etalSUD) misframing/ Pain mis mgt by previous clinicians / etal early Dx momentum – espec really early; sfx from Rx & interactions); one size fits none guideline faults.
Two different theories about dependence and withdrawal dictate different approaches:
- The Half-Life theory says the very short half-life of paroxetine and venlafaxine make these drugs more problematic. This leads to a withdrawal strategy that advocates switching from paroxetine to a long half-life drug like fluoxetine.
- The Potency theory says paroxetine and venlafaxine are worse because they are more potent SRIs. This leads to a switch to less potent SRIs like imipramine or dosulepin.
Either approach is helped by having access to treatment in liquid form.
a) Simple taper
Convert to a liquid form of the drug you are on. Reduce by a comfortable amount in weekly steps. This may mean reducing as little as 1 mg per week and being prepared to stop and stabilize if things get too difficult. Another approach is to reduce by 10% each week. For some people depending on the drug and their own physiology, there may be a need to go very slowly, others may be able to go faster.
b) Reduced potency approach
Switch to Imipramine or Dosulepin 100mg. Imipramine comes in 25mg and 10 mg tablets and also in liquid form. It is the first SRI. You could also combine half your dose of a potent SRI with 50 mg imipramine or dosulepin and then taper from the potent drug first.
c) The half-life approach
Convert the dose of SSRI you are on to an equivalent dose of fluoxetine liquid. Seroxat/Paxil 20mg, Effexor 75mg, Cipramil/Celexa 20mgs, Lustral/Zoloft 50mgs are equivalent to 20mg of fluoxetine liquid. Fluoxetine’s long half-life helps to minimize withdrawal problems. But some people become agitated on switching to fluoxetine. This might be caused by fluoxetine or because the substitution does not cover withdrawal from their original drug. If the agitation improves as fluoxetine is reduced it is more likely to be caused by fluoxetine. You could also combine half the drug you were on with a half dose of fluoxetine. The next step is to reduce gradually the dose of the original drug and after that to reduce the fluoxetine.
“Cochrane Schizophrenia Group’s register (May 2007) and MEDLINE (September 2007) were conducted for randomized, blinded studies comparing two or more of nine second-generation antipsychotics in the treatment of schizophrenia. 78 study Meta 13.5k patients combined result Tx Positive/Negative/Subscales/Dropout:
1.💊Olanzapine💊 proved superior to aripiprazole, quetiapine, risperidone, and ziprasidone.
2. 💊Risperidone💊 was more efficacious than quetiapine and ziprasidone.
3. 💊Clozapine💊 proved superior to zotepine and, in doses >400 mg/day, to risperidone. These differences were due to improvement in positive symptoms rather than negative symptoms. The results were rather robust with regard to the effects of industry sponsorship, study quality, dosages, and trial duration.” (AmJPsychi 2009)
All data were extracted by at least three reviewers independently. The primary outcome measure was change in total score on the Positive and Negative Syndrome Scale; secondary outcome measures were positive and negative symptom subscores and rate of dropout due to inefficacy. The results were combined in a meta-analysis. Various sensitivity analyses and metaregressions were used to examine bias.
2.2 Head To Head Neurolept Anti Psychotics
There were no significant differences between amisulpride and olanzapine (N=701), risperidone (N=291), and ziprasidone (N=122).
Aripiprazole was less efficacious than olanzapine in two studies sponsored by aripiprazole’s manufacturer (N=794, weighted mean difference=5.0, p=0.002). Two further studies found no significant difference compared with risperidone (N=372).
Clozapine was not significantly different from olanzapine (N=619), quetiapine (N=232), risperidone (N=466), and ziprasidone (N=146). Clozapine was significantly more efficacious than zotepine (N=59, weighted mean difference=–6.0, p=0.002). The comparison with risperidone was significantly heterogeneous due to one study sponsored by clozapine’s manufacturer (17) ; excluding the study did not change the overall results.
Olanzapine was significantly more efficacious than aripiprazole (N=794, weighted mean difference=–5.0, p=0.002), quetiapine (N=1,449, weighted mean difference=–3.7, p<0.001), risperidone (N=2,404, weighted mean difference=–1.9, p=0.006), and ziprasidone (N=1,291, weighted mean difference=–8.3, p<0.001). No significant difference between olanzapine and amisulpride (N=701) or clozapine (N=619) emerged.
Quetiapine was significantly less efficacious than olanzapine (N=1,449, weighted mean difference=3.7, p<0.001) and risperidone (N=1,953, weighted mean difference=3.2, p=0.003). There was no significant difference compared with clozapine (N=232) and ziprasidone (N=710).
Risperidone was significantly more efficacious than quetiapine (N=1,953, weighted mean difference=–3.2, p=0.003) and ziprasidone (N=1,016, weighted mean difference=–4.6, p=0.002). It was less efficacious than olanzapine (N=2,404, weighted mean difference=1.9, p=0.006). No difference compared with amisulpride (N=291), aripiprazole (N=372), clozapine (N=466), and sertindole (N=493) emerged.
There was no significant difference between sertindole and risperidone in two studies sponsored by sertindole’s manufacturer, one in treatment-resistant patients, which found results with risperidone to be 7 points better, the other without this criterion finding sertindole 3.5 points better (N=493), leading to significant heterogeneity.
Ziprasidone was less efficacious than olanzapine (N=1,291, weighted mean difference=8.3, p<0.001) and risperidone (N=1,016, weighted mean difference=4.6, p=0.002). No significant differences compared with amisulpride (N=122), clozapine (N=146), and quetiapine (N=710) were found.
Zotepine was less efficacious than clozapine (N=59, weighted mean difference=6.0, p=0.002).
Dosing reference to 10mg oral Dz.
6) The conversion factors listed are derived from pooled data in the peer-reviewed literature and pharmaceutical company product information.
4.0.1 Pseudo Opioid w/NE or 5ht kn (Tramal/Tapental)
Tramadol is a non poppy derived semi synthetic opioid-esk mu primary tg (tad more complex than that). Most opiates are antag at Mu (& delta/kapha – but also note Op1, Op2 & Op3 have started cropping up as novel receptor names. For whotf knows why). Naloxone is a primary ag at Mu [etal] (ANZCA a2018). GPro rec cAMP cascade interference is the text book key MOA for analgia. Quiet firing down k+ channel block w/some related CA++ voltage gate chnl restriction (inc cardiac AV node impacts…ish). To dose Heroin to equ is difficult because of purity problems, but if that is all you have to mix in for your tea, the schedules may assist. Not that Im advising that: but if pain is chronic and physicians are not assisting – a daily dose of something that does help, vs daily pain, is obviously the better choice. Pity there arent more physicians that first do no harm. I can not believe we are at a place where street dealers may be more reliable than physicians. (UNODC)(Opioid MOA QkRvw).
Tapentadol is a Jansen minor alt for money, w/claims that will never pan out regarding spine and NE. It is coming to a prominence from the opioid hysteria, claiming (like oxycodone before it), that it is less addictive and as potent. However, it is to be treated as ~double strength Tramal, w/ standard Tramal warnings. The 5ht element is apparently absent. The spine story sounds like bs intro to sales studies that will be poorly designed and selected for TGA ‘novel enough…but close enough to Tramal’ to cut red tape. Still in first decade of moderately common use. Appears effective.
And this CERTA biz is just puritanical insanity. And of course beyond ridiculous for the out pt. The only sane part is that they all ultimately involve opiates. Of course, if we just started there, no one would be left in pain. The back-flips thru internal reason hoops these young clinicians are doing is just incredible. But multiple Rx via impractical methods, & then an anyxiolytic (& an opiate…just delayed), instead of both effects from just an opiate up-front is where we are at. Until a few physicians & VIPs find out they or their wife had to go through this, & call their cousin the Governor. & call their law firm they just retired from. Because this is truly disgusting.
& inane. Anyway. That emotion is how you know this is a blog. My fav part is “away from symptoms based approach to pain, to a mechanistic” ie instead of asking is the pt in pain, we are now to explain to them why they arent. With charts. Fantastic ignorance of real world science gaps, and more ‘treat theory & numbers, not pts! Never pts!‘. If you can help it – dont touch them, talk to them or look at them.
Just tell them why they are wrong. & that what you did worked – they just dont understand the mechanistic approach to pain. It is their fault, really. Them & their under educated body. I mean, my Gawd. The most charitable thing to say would be it is a cash grab on the back of the opioid deaths. & hope that they do not practice anymore (*fingers crossed). Doesn’t reduce the harm however. But, unless you are screaming in pain, the theory work is fun. & luckily, we just got a double boarded emergency/ emergency-acupuncturist on the code team. So it looks like it is all pain-free & discomfort-free days ahead for everyone being tubed or dying! Heck, everyone everywhere! Everyone has access to 24h acupuncture, surely!
Why did we ever use pills for pain, when we could have been using nerve blocks & acupuncture at the drop of a hat! & ketamine, tricyclics & benzos! Totally reasonable.
More drugs will never be better. We do not understand anything new. Does ANY of that look new? All it looks like is patently incorrect. & anyone who has ever been stung by a bee or stubbed a toe can see that. All we are going to see with this “targeted” gobbledegook are new interactions & more idiosyncratic reactions, fixing a problem that isnt there – I mean clearly, right? Da-doi.
Look at that BS – emergency department level abdo pain out-pt d/c break out pain control “***oral acetaminophen or oral ibuprofen or both***“.
Have a look! That is also what it says for burns; for backpain (youve seen true back pain, with the grown men crying – sound right to you?); neuropathy (!!) (& shill some gabapentin, which does not work); all MSK; renal pain; & SICKLE CELL CRISIS. What a clear break through in targeted pain management.
F**king genius. @ least 711 also has Slurpies.
JC-R writes the “CounterPoint Steelman” column for ASQ: Presenting the best arguments, of the least popular positions, for rebuttable in the same issue.
JC-R is the research error and medical malpractice investigator for Letters and Science.
7.0 ~Lest We Forget~ (Malpractice & Methods)
Blood Crash Ref
Type i-iv Reaction Cascades