☼ MedRantRef+PsychRx+PainRxDQR

[upKeep2023]πŸ“‘Β πŸ‘ΎπŸŒ©βœ¨βš°πŸŒΌπŸŽ“πŸ„β€β™‚οΈπŸ’£πŸ‘ΉπŸ•΄πŸ‘¨β€πŸš€πŸ€ΉπŸŽͺπŸ‚πŸ¨πŸ₯‹πŸ΄β€β˜ οΈπŸŒ¦οΈπŸš€β˜”βŒšπŸš£πŸΆπŸŒ΄πŸŒˆπŸŽšπŸ§˜β€β™‚οΈπŸš”πŸβŒšπŸŽ‘πŸ’ˆ

“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.Β 
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.

Then:

Jump Link: NonOpioids | NeurolepticAntiPsychs |Β Benzodiazepines | Opioids | Malpractice | AntiDepressants |-RXKhb

1.0 Anti-Depressants
Consider disolverble (pseudo-soluable/ dispersable) flouroxetine for faster plasma spike to achieve symptom relief in w/d taper. [1][2][3]. Also liquid.
.
In choosing initial treatment:
.
“Escitalopram and sertraline stand out. Overall, escitalopram, mirtazapine, sertraline, and venlafaxine gave significantly more mood enhancement (efficacy) than fluoxetine or the other medications. Bupropion, citalopram, escitalopram, and sertraline were better tolerated than the other antidepressants. 🌠Escitalopram🌠and 🌠Sertraline🌠were found to have the best combination of mood enhancement (efficacy) and side effect acceptability”.(2009)(NNT20; NNT14 respectively). (8wk Acute. ~25k Head to Head Flouroxitine/control. Methods of inclusion & defns absent). [FamilyPracticeMed-Psychiatry 2009]
Β .
WeightGain
“Results evidenced that🍰amitriptyline🍰, 🍰mirtazapine🍰, and 🍰paroxetine🍰were associated with a greater risk of weight gain. In contrast, some weight loss occurs with fluoxetine and bupropion, although the effect of fluoxetine appears to be limited to the acute phase of treatment. Other compounds have no transient or negligible effect on body weight in the short term. However, the effect of each antidepressant may vary greatly depending on an individual’s characteristics and generally became more evident in the long term” (JClinPsy2010)
.
“522 trials comprising 116β€ˆ477 participants. In terms of efficacy, all antidepressants were more *effective than placebo, with ORs ranging between 2Β·13 (95% credible interval [CrI] 1Β·89–2Β·41) for 🍰🌠amitriptyline🌠🍰[but highest drop out rate & most weigh gain] and 1Β·37 (1Β·16–1Β·63) for reboxetine.
.
For *acceptability, only agomelatine(OR 0Β·84, 95% CrI 0Β·72–0Β·97) and fluoxetine [but least effective] (0Β·88, 0Β·80–0Β·96) were associated with fewer dropouts than placebo, whereas clomipramine was worse than placebo (1Β·30, 1Β·01–1Β·68).
.
Β In *head-to-head studies, agomelatine, amitriptyline,Β  escitalopram🌠, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1Β·19–1Β·96),
.
For *acceptability, agomelatine, citalopram, 🌠escitalopram🌠, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0Β·43–0Β·77),
.
*least efficacious drugs whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were theΒ  (0Β·51–0Β·84).
.
*highest dropout rates: **amitriptyline**, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxinehad theΒ  (1Β·30–2Β·32).“
.
***(82%) of trials were rated as moderate-high risk of bias, and all of the quality of evidence was moderate to very low. Lancet, 2018
.
When all trials were considered, differences in ORs between antidepressants ranged from 1Β·15 to 1Β·55 for efficacy and from 0Β·64 to 0Β·83 for acceptability, with wide CrIs on most of the comparative analyses.
.
1 anti d
.
2 antid
Weight Gain Amounts
019 weight gain in ADeps - JAMA Psychi
ADep + weight gain iiADep weight gain rec theoryADeps Ppain & BMI+Smoking
+a01909 weight gain ADep at a glsnce
+01908 Mean weight dif in kg
Consultant,v53-i3, 2013/JAMA Psychiatry,Β 2014/ JObesity, 2011 – “iatrogenic weight gain in kg/mth”
Neuropathic Pain (Including fibromyalgia)
AmitriptylineΒ has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment – Cochrane, 2015
GabapentinΒ ..Around [3.5] out of 10 ..[50% pain reduction] cf w/ [1.5] out of 10 for placebo..may experience adverse events – Cochrane, 2017
Tramadol evidence of benefit from tramadol was of low or very low quality, meaning that it does not provide a reliable indication of the likely effect. – Cochrane, 2017
Opioids Intermediate-term studies demonstrated significant efficacy of opioids over placebo..chronic neuropathic pain is subject to considerable uncertainty. Reported adverse events of opioids were common but not life-threatening. (*Prior to opioid hysteria.) – Cochrane, 2013
1.2 Taper & Switching AntiDeps [+1 Hb][2][3Rxisk]

Two different theories about dependence and withdrawal dictate different approaches:

  1. 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.
  2. 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.

Tapering

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.

AntiD dose redux schedule taper
1.3 Half Lives & Dose Wash Out Before Fluoxetine
wd time table half life a
wd time table half life b
abcde
1.4 Cannabinoid Rec Review 018
+1 01812 CBD multi Rec ActivityCanabanoid recs + fn Rx Tgt
1.5 AntiHistamines & AntiEmetics QkRef – Sedation + MOA[h1agNIH]
++01910 AHist and sedation v cholergic act
+++ Hist rec A+++ Hist rec B
+++ Hist rec B
AntiEmeticsrhinitis ahists
2.0 Neuroleptics (Geni/ii) – All Pretty Toxic Poisons:
Take Them Only for Serious Conditions (ie Not Insomnia, Anxiety etal); Try Everything Else First; Then Only If You Need Them (You Will Have Woken Up On Them At Least Once Very Likely) *(See Ed Nb I)(RxISKMinDoseGuide)(HalfLives)FirstBreakCdr:[1][2][3][4]
.

“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.πŸ’ŠOlanzapineπŸ’Š proved superior to aripiprazole, quetiapine, risperidone, and ziprasidone.

2. πŸ’ŠRisperidoneπŸ’Š was more efficacious than quetiapine and ziprasidone.

3. πŸ’ŠClozapineπŸ’Š 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.

50yrsChlorpromazine(NPsychiDxTx2007)GenPrX

2.1 Inject & Forget Neurolept Anti Psychotics: [2]

Long-Acting_Injectable_Antipsychotics_A_Practical_Guide_for_Prescribers_-_Psychopharmacology_Institute_-_2018-02-11_11.41.08

Long-Acting_Injectable_Antipsychotics_A_Practical_Guide_for_Prescribers_-_Psychopharmacology_Institute_-_2018-02-11_11.47.21

ab

(Psychopharmmacology Institute 2018)(RXisk)

2.2 Head To Head Neurolept Anti Psychotics

Amisulpride

There were no significant differences between amisulpride and olanzapine (N=701), risperidone (N=291), and ziprasidone (N=122).

Aripiprazole

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

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

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

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

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.

Sertindole

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

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

Zotepine was less efficacious than clozapine (N=59, weighted mean difference=6.0, p=0.002).

.

Weight Gain

Neurolept weight

3.0 Benzodiazepines

Dosing reference to 10mg oral Dz.

benzodiazapine-conversion-table-orig_orig


.
4.0 Opioids
.

methadone_to_heroin_equivalence_-_General_Practice_Notebook_-_2018-02-24_14.12.09

a opioid-dose-equivalence.pdf_-_2018-02-06_05.32.49

b opioid-dose-equivalence.pdf_-_2018-02-06_05.33.21

1) This opioid dose equivalence table is intended for comparison of different opioid regimens in individual patients or in patient cohorts.
2) Caution is required if opioid dose equivalence tables are used to guide opioid switching, as the administration of a calculatedβ€˜equivalent’ dose of the replacement opioid may lead to overdosage.
3) It should be noted that there is considerable variability in pharmacokinetics and pharmacodynamics of the different opioids, within and between individual patients. In addition interactions with non-opioid drugs can strongly influence opioid pharmacokinetics.
4) Modified-release formulations can be sub-classified as delayed- or extended- release. Extended release of a drug can be achieved using sustained- or controlled-release delivery systems. When the opioid regimen includes modified- and immediate-release preparations, both should be included in calculation of the oMEDD.
5) Methadone, fentanyl lozenges and neuraxial opioids are not included in this table due to their complex and variable pharmacokinetics.

6) The conversion factors listed are derived from pooled data in the peer-reviewed literature and pharmaceutical company product information.

Β  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).Β  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.

Tapental dese equ
Tapentadol Jansn Tramal NE Flavor Pseudo-OpioidTaptadol ramp uptptadol .5 of trma
gen chartopioid metabolism
Β .

5.0 Non Opioid
.
5.1 Anti Spasmodic & Muscle Relaxants
.
Most of these are centrally GABAa/b benzo/barb variants (or actual, by dose increase threshold). Including the weak micro-whatever theories behind gabapentin & pregabalin. All of which means they are pretty much all: 1) still addictive; 2) similar contraindications to opiates; 3) not much better than opioids addiction wise at all; 4) still “abuse potential” (ie they do work to bring relief, if dose is high enough); 5) but not as good for pain as the opioids. & some pts report the withdrawal is even worse than heroin (links below). Yet under the opioid hysteria here we are.
Β .
Alcohol & opiate interaction standards apply, of course. In addition to Hypericin/Hyperforin (St Johns Wort) warning, because it interacts with everything through Bogart metabolism alting plasma concentration.
Β .
Acetylcholine (recNic/muscAntag)/alpha adrenal & even subP gets a mention with some of them. This is generally periphery – though none of it is strictly pain relief. How a systemic ACH Rx knows magically which muscles are spastic, & targets them, w/o, oh idk, stopping heart & lung while leaving you a pile of jello on the floor, has never really been explained. More likely they dont work, unless applied directly to the target area. Sfx do present though.
.
And ask any pain specialist about the usefulness of topical analgesics for a non topical pain presentation.Β In nearly all cases the suggestion is just not seriously targeted at reliving pain to full function. How does it get where it needs to go?Β & where is it metabolized? It is not credible if you are seriously aiming for optimal care.Β 
.
When there is a list posited to play a role like this, though likely partly true, most of all it just means we dont really know. & none of them stand out as particularly superior to opioids – nor particularly safer in the trade off – at this time. Nor technically analgesics at all.
Β .
Also, marijuana proper or the oils would be included here. Im w/o opinion on this application at this time. Though I do have pts on trials who will be providing feedback over the next 12months.
.
Central Acting Muscle_Relaxers_
Antispazmotics
a2018 – Au MSK PBS / PBS by BodySys / AntiRheumatics/ NIHCfEfficacyMSKSysRvw008 / RxMSKDoseSfxAmFamPhys008 / CochraneMSK012 A Backpain003 B (says what they always say)
Β 5.1.1 NSAIDs
+++ nsaid dosing++dosage iinsaids dosensaids
.
5.2 Non-Opioid Full Inclusion Schedule (Questionable – but official)
.
Yep. So apparently, 7 Panadol (acetaminophen/paracetamol 500) is the same as 10mg’s of morphine. Yeah fine. Sounds right. And then you’d need about 12 Β Nurofen (ibuprofen 200) to equal 7 Panadol? Sure, why not. This is why pretending there is an opioid epidemic will be just fine. All this great real world science. No One believes this, by the way, if treating themselves for pain. *(NSAIDDoseCeiling 2018; StandAlone Paracetamol/Acetaminophen For Pain Is Good For…The Bin 2018)
Β .

a morphine All Rx Equ.jpg

b morphine All Rx Equ

c morphine All Rx Equ

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.

+1 01808 opioid Free Push ED BS

opioid alts 1

opioid alts 2

++1 Opioid_Receptors_018 review

AU EM Guidelines 018/ ALTO 018

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

..

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)

*Ioannidis, M.D., D.Sc (Stanford): Individualized Healthcare, Big Data & Evidence-Based Medicine – Contradictions or Compassionate Companions? (2018)

*Concerns Regarding Malpractice Runs Into The Billions (Pharma Settlements)

*Forensic Psychiatrist Dr Yol Lucire, PhD MD: Moral Panic & Prescribing Behaviors

*Ethics Abuse In Human Pharmacological Research (UTulsa MedLaw) – C.Elliott

*Dr Joanna Moncrieff: Chemical Cure Myth – Politics of Psychiatric Drug Treatment

*Dr David Healy: The Pharmaceutical Python (Yale Psychiatry)

*Ivan Oransky, MD: Fraud & Retractions In Medical Science – (NYU)

*Prof of Med & Statistics Ioannidis: Medical Research Is Broken (Stanford/CalTech)

*Neuropsychopharmacology Prof David Nutt (Imperial College London)

*Diagnostic and Therapeutic Controversies – All Faculty (EmergencyMed CCME)

*UNM Psychiatry GR: Succeeding & Psychotic – Mark Vonnegut, M.D. (Harvard)

*Ioannidis (Stanford) on nutritional research 2018

**Diagnostic & Medical/Research Error List**

[JC0181101]

Immune QkRf:

 

SpectoGrams (Wellington)

+++1 simplified full guide to immune

Hydroxychloroquin invitro (possible) moa tgt actions
2020-04a in vitro hydroxy chloro quinalone list of antiicrobial obs table
*RUImuneFdmtlHb(inate+B)
*RUImuneAutoImuneHb
*RUImuneHb(Tcel+Sigl)

*EtOHAutoImuneRv
*nihFulAnoyingGlos

Become part of the journey. You will be welcomed by the others and your comments thoughtfully considered.

Fill in your details below or click an icon to log in:

Gravatar
WordPress.com Logo

You are commenting using your WordPress.com account. ( Log Out /  Change )

Google photo

You are commenting using your Google account. ( Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. ( Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. ( Log Out /  Change )

Cancel

Connecting to %s