Posts Tagged ‘CYP450’

Tranquility or Agitation? There’s a drug for that!

Monday, April 25th, 2022

Agitation, as with many English words, has multiple definitions. Here are a few:
1. moving back and forth with an irregular, rapid, or violent action
2. a feeling of being restless
3. a state of excessive tension and irritability
4. a state of anxiety, emotional disturbance, worry, upset, or nervous excitement
[From Latin agitare, put into motion]

Agitation is a side effect of various psychotropic drugs, such as psychostimulants given to children for so-called ADHD; newer antidepressants such as SSRIs; antipsychotics often called major tranquilizers; anti-anxiety drugs often called minor tranquilizers.

So, pretty much all psychiatric drugs, often prescribed to reduce agitation, have a side effect of agitation. Counter-productive, wouldn’t you say?

The psychiatric billing bible, the Diagnostic and Statistical Manual of Mental Disorders (DSM), specifies some diagnoses related to agitation:

 — Restless legs syndrome
 — 54 individual diagnoses using the word “anxiety”
 — High expressed emotion level within family
 — Adjustment disorder, With mixed disturbance of emotions and conduct

Pretty much anybody, then, can be diagnosed with some form of agitation or anxiety and prescribed one or more psychiatric drugs which have the potential to exacerbate the agitation.

The Latest Agitation Drug

On April 6, 2022 the US Food and Drug Administration (FDA) approved BioXcel Therapeutics dexmedetomidine (Igalmi™) sublingual film for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

Dexmedetomidine is a sedative whose safety and effectiveness cannot be established beyond 24 hours from the first dose, usually used to anesthetize a patient or animal before surgery. It inhibits the release of norepinephrine in the brain, stopping propagation of pain signals. They don’t really know how it “works” for agitation, other than the obvious fact that it knocks you out. It’s mostly eliminated from the body within hours. It’s metabolized in the liver by Cytochrome P450 (CYP450) enzymes, so the side effects can be exacerbated by abnormal CYP450 metabolism which can lead to a toxic level causing acute agitation.

The most common side effects (incidence ?5% and at least twice the rate of placebo) were sleepiness, burning or prickling sensations, oral numbness, dizziness, dry mouth, and low blood pressure.

Since it is self-administered by placing the film under the tongue, it’s used by an individual to knock themselves out when they are having an anxiety attack.

Psychiatrists promoting this “treatment” are ecstatic about it, since the patients can knock themselves out whenever they feel the need.

If you feel the need, please contact your local, state and federal representatives and let them know what you think about this.

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Titration Titillation

Monday, January 10th, 2022

Titration is the process of adjusting the dose of a drug for the maximum benefit that can be obtained without any adverse effects. When a drug’s recommended dosage has a narrow therapeutic range, titration is especially important, because the range between the dose at which a drug is effective and the dose at which side effects occur is small. The starting dose is very low, and then increased regularly until the symptoms subside, or the recommended maximum dose is achieved, or side effects occur.

[Titrate ultimately derived from Latin titulus, “inscription, label, title”.]

When changing to a different medication, sometimes one can be stopped and the other then started without overlap. However, with some there needs to be overlap, called cross-titration.

Since some psychiatric drugs may take weeks or months to demonstrate an effect (or an adverse reaction), titration is pretty much just guesswork. There is a general lack of evidence regarding the impact of titration rate on clinical outcomes. There are no specific recommendations on what titration rate is optimal for achieving rapid response while minimizing adverse effects.

The half-life of a drug is the time it takes for the amount of a drug’s active substance in the body to reduce by half. Psychiatric drugs are metabolized in the liver by Cytochrome P450 enzymes in order to be eliminated from the body. A person genetically deficient in these enzymes, or who has an ultrarapid drug metabolism, or who is taking other (legal or illegal) drugs that diminish CYP450 enzyme activity, is at risk of a toxic accumulation of the drug leading to more severe side effects.

Most antipsychotics have an average half-life of 1 day or longer; it can take up to 5 days or more for patients to reach steady-state concentrations with the same daily dose. One would not generally want to titrate the dose until a relatively steady-state concentration was reached.

One recent retrospective study of 149 hospitalized patients on antipsychotics was relatively inconclusive; it was unclear to what extent titration rate either improved symptoms or reduced length of hospital stay. Patients who continued to have their dose increased were less likely to adhere to treatment, due to increasing adverse reactions. Also, delayed adverse effects may occur if dose increases occur sooner than necessary.

Since the 1960s, there has been a large push for patients in psychiatric hospitals to be discharged as quickly as possible. In such an inpatient setting, pressure may be put on prescribers to titrate antipsychotics quickly with the hopes of reducing length of stay and hospitalization costs.

All this goes to show the general lack of predictability in the administration of psychiatric drugs, although it doesn’t even begin to address the fact that these drugs are generally addictive and harmful, and that they are prescribed for fraudulent diagnoses.

One must also keep in mind that the psychiatric industry generally pushes psychotropic drugs without regard to these considerations. This is the direct result of the unscientific psychiatric diagnoses perpetrated by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) which fraudulently justifies prescribing these harmful drugs for profit in the first place.

The real problem is that psychiatrists fraudulently diagnose life’s problems as an “illness”, and stigmatize unwanted behavior or study problems as “diseases.” Psychiatry’s stigmatizing labels, programs and treatments are harmful junk science; their diagnoses of “mental disorders” are a hoax – unscientific, fraudulent and harmful. All psychiatric treatments, not just psychiatric drugs, are dangerous because they preclude finding out the real causes of mental trauma and treating those.

At best one might consider psychotropic drugs as “first aid”; they never have and never will cure any mental trauma. While the patient may be lulled into a temporary sense of wellness, whatever condition has caused the symptom is still present and often growing worse. Psychiatrists have deceived millions into thinking that the best answer to life’s many routine problems and challenges lies with the “latest and greatest” psychiatric drug.

Find Out! Fight Back!

Marketing of Madness
Marketing of Madness

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Qelbree, The Newest ADHD Drug

Monday, June 21st, 2021

The U.S. Food and Drug Administration (FDA) approved a new drug April 2, 2021 for treatment of the fraudulent “disease” Attention Deficit Hyperactivity Disorder (ADHD) in children ages 6 to 17.

Like many other psychiatric drugs, this one also carries an FDA warning:”Qelbree may increase suicidal thoughts and actions in some children with ADHD, especially within the first few months of treatment or when the dose is changed.”

Qelbree (generic viloxazine hydrochloride) is a non-stimulant drug, although it is a Selective Norepinephrine Reuptake Inhibitor (sNRI), which means that it is really an antidepressant and is similar in operation to other ADHD drugs such as Strattera. The bottom line is that this class of drugs messes with neurotransmitters in the brain, and taking them is playing Russian Roulette with your brain.

Qelbree is an inhibitor of several Cytochrome P450 enzymes, which may intensify the drug’s side effects especially in combination with certain other drugs.

And again, like other similar psychiatric drugs, “The mechanism of action of viloxazine in the treatment of ADHD is unclear.“

There is no valid ADHD clinical test for children. There is no valid ADHD clinical test for adults. The ADHD diagnosis does not identify a genuine biological or psychological disorder. The diagnosis is simply a list of behaviors that may appear disruptive or inappropriate, and is essentially just an opinion.

No one denies that people can have difficult problems in their lives, that at times they can be mentally unstable, subject to unreasonable depression, anxiety or panic. Mental health care is therefore both valid and necessary.
However, the emphasis must be on workable mental healing methods that improve and strengthen individuals and thereby society by restoring people to personal strength, ability, competence, confidence, stability, responsibility and spiritual well-being. Psychiatric drugs and psychiatric treatments are not workable.

ADHD Newborn

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Cap It Off With Caplyta

Monday, September 21st, 2020

Emerging from a cloud of regulatory questions and mixed clinical results, Caplyta (generic lumateperone) an atypical antipsychotic from Intra-Cellular Therapies, Inc. was given FDA approval 20 December 2019, and is now being heavily marketed. There are over a dozen of these second-generation antipsychotics, with varying activity at the brain receptors for various neurotransmitters.

It is hardly clear whether lumateperone has any advantages over other antipsychotic drugs. The primary reason for researching and releasing another atypical antipsychotic is to try to reduce the side effects, rather than to actually eliminate the symptoms, since no one really knows what causes these symptoms. The manipulation of neurotransmitters in the brain is just a guess, unfounded by any real understanding, just as the actual causes of so-called schizophrenia (psychiatry’s “For Profit Disease”) are not understood.

Side Effects of this dangerous drug include: stroke, neuroleptic malignant syndrome, tardive dyskinesia, diabetes, low white blood cell count, low blood pressure, falls, seizures, sleepiness, trouble concentrating, high temperature, difficulty swallowing, withdrawal symptoms in newborn babies exposed to Caplyta during the third trimester, pruritus (itchy skin), rash, urticaria (hives), increased mortality in elderly patients with dementia-related psychosis.

Patients are urged to avoid Cytochrome P450 (CYP3A4) inducers or inhibitors, since these may exacerbate the adverse reactions, causing violence and suicide.

List Price: $44 per 42mg capsule, with a peak sales estimate of $60 million in 2020 and $400 million by 2024. There may be conditions for insurance approval; for example, UnitedHealthcare may require the failure, contraindication, or intolerance to three other atypical antipsychotics before giving approval to pay for the use of Caplyta.

The antipsychotic activity of Caplyta is thought to be mediated through a combination of antagonism of serotonin receptors and antagonism of dopamine receptors in the brain, however the actual mechanism of action of Caplyta in schizophrenia is unknown.

Clinical trial results were measured by the opinion of a clinician observing or asking the patient about their feelings. The results require cautious interpretation and could represent chance findings. One phase III trial showed some symptomatic improvement and another phase III trial failed to show any improvement over placebo.

Obviously use this drug at your own serious risk, and insist on Full Informed Consent.

The real problem is that psychiatrists fraudulently diagnose life’s problems as an “illness”, and stigmatize unwanted behavior as “diseases.” Psychiatry’s stigmatizing labels, programs and treatments are harmful junk science; their diagnoses of “mental disorders” are a hoax – unscientific, fraudulent and harmful. All psychiatric treatments, not just psychiatric drugs, are dangerous.

It is vital that patients watch the video documentary “Making A Killing – The Untold Story of Psychotropic Drugging“. Containing more than 175 interviews with lawyers, mental health experts, the families of psychiatric abuse victims and the survivors themselves, this riveting documentary rips the mask off psychotropic drugging and exposes a brutal but well-entrenched money-making machine. The facts are hard to believe, but fatal to ignore.

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Schizo Christmas Present from the FDA

Sunday, December 29th, 2019
The US Food and Drug Administration (FDA) finally approved the new antipsychotic drug lumateperone (Caplyta, from Intra-Cellular Therapies, Inc) on December 23, 2019 for treatment of schizophrenia in adults, in spite of previously canceling its review because of mixed results in testing, which were blamed on positive responses to placebos.

As with other antipsychotics, lumateperone includes a boxed warning that elderly patients with dementia-related psychosis are at an increased risk for death.

Also as with other antipsychotics, the mechanism of action is unknown — they’re just guessing about how it is supposed to “work.” It plays Russian Roulette with serotonin, dopamine and glutamate (another neurotransmitter) in the brain.

It has all the usual possible side effects – neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia, diabetes, weight gain, sedation, increased risk of falls, seizures, infertility, etc.  Newborns exposed to antipsychotic drugs during the third trimester of pregnancy may suffer withdrawal symptoms.

Since cytochrome P450 enzymes such as CYP3A4 are involved in its metabolism in the liver, a person’s genetic abnormality with these can lead to the drug or its metabolites reaching a toxic level in hours or days, correlating with the onset of severe side effects. One is also ill-advised to drink grapefruit juice with this drug because it strongly inhibits the CYP3A4 enzyme, again increasing the risk of serious adverse reactions.

Of course, psychiatrists attribute any attempts at suicide to the underlying diagnosis and not to the drugs.

Speaking of the Underlying Diagnosis

Today, psychiatry clings tenaciously to antipsychotics as the treatment for “schizophrenia,” despite their proven risks and studies which show that when patients stop taking these drugs, they improve.

The late Professor Thomas Szasz stated that “schizophrenia is defined so vaguely that, in actuality, it is a term often applied to almost any kind of behavior of which the speaker disapproves.”

These are normal people with medical, disciplinary, educational, ethical or spiritual problems that can and must be resolved without recourse to drugs. Deceiving and drugging is not the practice of medicine. It is criminal.

Any medical doctor who takes the time to conduct a thorough physical examination of a child or adult exhibiting signs of what a psychiatrist calls Schizophrenia can find undiagnosed, untreated physical conditions. Any person labeled with so-called Schizophrenia needs to receive a thorough physical examination by a competent medical—not psychiatric—doctor to first determine what underlying physical condition is causing the manifestation.

Any person falsely diagnosed as mentally disordered which results in treatment that harms them should file a complaint with the police and professional licensing bodies and have this investigated. They should seek legal advice about filing a civil suit against any offending psychiatrist and his or her hospital, associations and teaching institutions seeking compensation.

No one denies that people can have difficult problems in their lives, that at times they can be mentally unstable, subject to unreasonable depression, anxiety or panic. Mental health care is therefore both valid and necessary. However, the emphasis must be on workable mental healing methods that improve and strengthen individuals and thereby society by restoring people to personal strength, ability, competence, confidence, stability, responsibility and spiritual well–being. Psychiatric drugs and psychiatric treatments are not workable.

For more information, click here to download and read the full CCHR report “Schizophrenia—Psychiatry’s For Profit ‘Disease’“.
Calvin and Hobbes

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You May Be Seeing Things That Aren’t Really There

Monday, August 27th, 2018

But You Can See The Wool Being Pulled Over Your Eyes

Hallucinations and delusions are possible complications of Parkinson’s disease (PD). They are often referred to as PD psychosis. It’s estimated to occur in up to 50 percent of people with PD.

Hallucinations during PD can be frightening and debilitating. There are many factors that can contribute to hallucinations in people with PD, but the majority of cases occur as side effects of PD drugs.

Psychotic symptoms are related to high levels of a neurotransmitter known as dopamine, which is often one of the adverse reactions of psychiatric drugs.

There are many drugs that may contribute to hallucinations or delusions in people with PD, including sedatives and anti-seizure drugs.

Another danger is that a person experiencing PD psychosis may be misdiagnosed with schizophrenia and prescribed antipsychotics which may cause serious side effects and can even make hallucinations and delusions worse.

In 2016 the U.S. Food and Drug Administration (FDA) approved the antipsychotic drug pimavanserin (Nuplazid) specifically for use in PD psychosis because it does not alter levels of dopamine in the brain as much as other antipsychotics.

However, Acadia Pharmaceutical’s antipsychotic drug pimavanserin is now facing public scrutiny and fiscal uncertainty after a report from CNN in April 2018 detailed the deaths of more than 700 patients prescribed this drug since June 2016. You may be seeing advertisements for pimavanserin (Nuplazid) now in an attempt to reverse its negative publicity.

The exact mechanism of action of pimavanserin is unknown; however, it messes with the level of serotonin in the brain like other antipsychotics do. Special dosing requirements are necessary when other drugs being given along with pimavanserin have strong CYP450 interactions.

Nuplazid carries the black box warning “Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.” It also has a known adverse reaction of hallucinations with 5% of those taking it, which is exactly what it is supposed to prevent. Since no one knows how it is really supposed to work, it is just a guess based on what is observed during clinical trials, with the hope that its side effects won’t be too drastic, and that enough of it can be sold before the outcry against its adverse side effects becomes loud enough to ban it.

It’s just another harmful psychiatric drug whose purpose is to make money at the expense of vulnerable people, and make more patients for life due to its damaging side effects. Click here for more information about these harmful psychiatric drugs.

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