Handbook of Critical Psychiatry Chapter 8: Depression and Mania (Affective Disorders) (Part Eleven)

Editor’s note: In the coming months, Mad in America will be publishing a serialized version of Peter Gtzsches’ book,Handbook of critical psychiatry. In this blog he discusses the harmful effects of lithium and the anti-epileptic drugs used for bipolar disorder. A new section of the book is published every Monday and all chapters are archived Here.

Lithium damage

Llithium is a highly toxic drug which requires close monitoring of the serum level. The FDA warns that lithium toxicity can occur at doses close to therapeutic levels.⁴³⁷

This fact was ignored in a textbook which stated that lithium is generally well tolerated and its harms are few and far between.^18:115 If true, it is surprising that 40% of patients discontinue treatment prematurely, which the book refers to on the same page.^18:115

Another textbook respected the evidence. He mentioned that the most common adverse effects are polydipsia, polyuria, weight gain, hand tremor, gastrointestinal symptoms such as nausea, dyspepsia and diarrhea, minor edema and skin reactions, and that mental impairments include difficulty concentrating, memory impairment and decreased vitality and creativity.^17:662 The book noted that long-term damage is more serious: up to 10% of patients have morphological changes in the kidneys, 1% have irreversible kidney damage, and in rare cases hypothyroidism and teratogenicity occur.^17:662 A third textbook confirmed the risk of malformations.^16:301

In the package inserts, patients and their families are warned that the patient should stop lithium therapy and contact the doctor in case of diarrhea, vomiting, tremor, mild ataxia (unexplained although few patients know it means loss of control body movements), drowsiness or muscle weakness. The risk of lithium toxicity is increased in patients with renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, and in patients taking medications that can affect renal function, such as certain antihypertensives, diuretics, and pain relievers for arthritis. A great many drugs can change serum lithium levels, making lithium very difficult to use safely.⁴³⁷

There are other serious harms, such as lithium can cause heart conduction disturbances.^16:299

One book stated that stopping lithium therapy increases the risk of a new manic episode beyond the risk associated with the natural course of the disease prior to lithium therapy.^16:589 There was no reference to this statement and, as with other psychiatric drugs, it is likely that what is seen when lithium treatment is stopped is withdrawal effects rather than relapses. The only relevant reference in this section was not to lithium, but to a meta-analysis network of pills for psychosis in patients with schizophrenia.²¹⁸

Lithium is similar to psychosis pills in its effects, which include emotional dulling, apathy, decline in cognitive functioning, and impoverished lives with little social contact.^5.135 Patients coming off lithium may end up worse than ever,³ and the time to a recurrence after lithium withdrawal is many times shorter than it is naturally.⁴²⁷

Much like depression and schizophrenia, bipolar disorder now appears to be taking a more chronic course due to the medications used. In the past, about a third of manic patients had three or more episodes in their lifetime, but now it’s two-thirds, and depression pills and ADHD medications can cause a rapid cycle of ups and downs.⁵

The list of serious damages that lithium can cause is very long and frightening,⁴³⁷ and we don’t know if the brain damage is reversible.^11:204 This is not a drug I would recommend to anyone.

Pills for psychosis, antiepileptics and ECT

Textbooks recommended that instead of lithium, pills for atypical psychosis or antiepileptics could be used.^{16:297,18:241,7:220 pm} One textbook did not recommend lithium as a first choice for mania, instead recommending pills for psychosis, which could be combined with benzodiazepines to avoid large doses.^18:114 I doubt there is a good reason not to use benzodiazepines alone as the idea of ​​curing mania is to calm the patient which is a matter of dose.

This book noted that patients with mania and depression can usually be treated effectively with modern psychotropic drugs, which were said to prevent relapses in most patients, but there was no reference for this statement.^18:110 which is false.⁴³⁸ Later it was stated that modern drugs meant pills for psychosis.^18:116

As noted earlier, modern is an inappropriate term to use, as it suggests that new drugs are better than the old ones, which is rarely the case, and psychosis pills prevent nothing other than letting patients live longer lives. normal and productive. This book also stated that, with medication, most manic episodes resolved in 6-8 weeks, while an untreated manic episode lasted anywhere from a few months (most often) to several years.^18:115 Obviously, this statement was not derived from placebo-controlled studies.

One book noted that there is no evidence for the use of antiepileptics for treatment-resistant depression.^16:275 The same book stated that valproate has a well-documented antimanic effect and that lamotrigine is approved for prophylaxis.^16:302 Unsurprisingly, doctors think AEDs work for mania, since anything that knocks people down works for mania. The main effect of antiepileptics is that they suppress emotional reactivity by numbing and sedating people.¹³⁵

Like most other psychiatric drugs, antiepileptics are used for just about everything. I have seen many patients walk in the door of psychiatry with a variety of initial diagnoses, most often depression or nothing that qualifies for drug treatment, all ending up receiving a gruesome cocktail of drugs that include antiepileptics. Antiepileptics not only celery people, they can also make them manic^390.439 and thus giving patients a false diagnosis of bipolar.

The trial literature has been distorted to an extreme extent. For gabapentin (Neurontin), for example, trials and statistical analyzes and positive outcomes were selectively reported; patients were improperly excluded or included in the analyses; and spin made negative results appear positive.^440,441

Bias has already been introduced at the design stage, such as using high doses leading to unmasking, although Pfizer has acknowledged that unmasking due to adverse events could corrupt the validity of studies. The last level of corruption was carried out by ghostwriters and corporate bosses: we would need to have editorial control; The results, if positive, will be published; We’re using a medical agency to put together the document that we’ll show Dr. Reckless. We don’t let him write it himself.

Gabapentin was only approved for people with treatment-resistant epilepsy, but Warner-Lambert, later bought by Pfizer, illegally promoted it and sold it for just about everything, including ADHD and bipolar disorder.^6:151 Nearly 90% of influential thought leaders were willing to promote gabapentin at meetings after being briefed on the company’s promotional strategies. A company executive told a Neurontin salesman about everything… I don’t want to hear that safety bullshit.⁴⁴² The company has insisted on pushing doctors to use much higher doses of Neurontin than approved, meaning more deaths.

In 2010, a jury found Pfizer guilty of organized crime and conspiracy.⁴⁴³ Six years earlier, Pfizer paid $430 million to settle charges that it fraudulently promoted Neurontin for unapproved uses.⁴⁴⁴

We have seen similar problems with other medications. For lamotrigine, seven large negative studies remained unpublished and invisible to the public, while two positive studies were published.^7:193

Epilepsy medications have many harmful effects, for example 1 in 14 patients treated with gabapentin develop ataxia.⁴³⁹

A textbook stated that some antiepileptics can be used for prophylaxis of bipolar disorder.^18:242 There were no references, but systematic reviews do not appear to provide support for this claim.^445,446 I did not think it was worth going any further, as the evidence in this area is of such poor quality that it is a major undertaking to do a systematic review of each agent, and there are many AEDs. Furthermore, antiepileptics are so toxic that I doubt their use can be justified.

A textbook described several harms with antiepileptics,^17:663 but not the most important, which is that these drugs double the risk of suicide. The FDA package insert for pregabalin (marketed to great success by Pfizer under the alluring name Lyrica) mentions a meta-analysis of 199 placebo-controlled clinical trials of 11 antiepileptics that showed an adjusted hazard ratio of 1.8 (from 1 .2 to 2.7) for suicidal thoughts or behavior.³⁹⁰

Mood stabilizer is a euphemism that psychiatrists have never defined. They usually mean antiepileptic drugs and lithium. Eli Lilly also calls olanzapine a mood stabilizer,⁷ which is Orwellian Newspeak. Psychosis pills don’t stabilize anything, but they calm people down, make them passive, and make it harder for them to live a normal life. This term should be dropped, as it is highly misleading.

This textbook admitted 345 pages later that there is little evidence of an effect of antiepileptics, but that they are still used to some extent.^16:577

I would not recommend AEDs for any mental disorder.

One book stated that ECT is the only monotherapy effective in over 60% of patients.^16:302 Another book went even further and claimed that 80% of patients with treatment resistant depression responded to ECT,^17:360 which is a meaningless statement, since there is no control group.

One book stated that there is great potential in preventing more depression and mania by offering a combination of drugs and psychoeducation as soon as a bipolar diagnosis has been made.^16:307 There is no reliable evidence that medications can prevent relapses.

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To see the list of all cited references,Click here.