What Do We Know About Mental Illness? Part I

What do we know about mental illness?  I will start here with a disclaimer.  I am not a psychi-
atrist, psychologist, neuroscientist or any type of professional in the field.  What I am is a curious individual who has had three major depressions and a mother who was given a lobotomy and subsequently institutionalized.  I want to know more.  Indeed I have a personal stake.  So I have begun a journey to seek and  sift through available information and to see where that takes me.

The simple answer to the question, what do we know about mental illness, is not much.  We do not know why a particular drug or therapy is effective or ineffective with any particular individual.  We do not know the sequence of chemical/biological changes which occur; we only know any particular drug or therapy is of limited effectiveness, that is, it does not work for everyone.  Since the introduction in 1950 in the United States of the first antipsychotic medication for schizophrenia, chlorpromazine, known more commonly by its trade name Thorazine, there have been at least 15 others introduced.  WebMD lists at least 55 medications used to treat depression.  It often takes an individual suffering from depression several tries with different drugs to find one that works.  And, there are what are termed drug-resistant patients which is in part what fuels the on-going research on new drugs and treatments.

The good news is that such research is taking place and that there is research comparing the effectiveness of existing drugs.  In 2013 the British medical journal The Lancet published an article comparing the effectiveness of the major antipsychotic drugs in treating schizophrenia.  All were better than a placebo; chlorpromazine was more effective than two other anti-psychotics, about as effective as two others and 12-16% less effective than a further three.  (Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M (September 2013). “Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis”. The Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3.).

There needs to be more such research and its results more widely available to the public, particularly those suffering from mental illness and their immediate families and friends.

And it has just been announced that an expert panel has recommended to the FDA the approval of a new type of drug for severe depression, particularly depression involving suicidal thoughts.  While past drug development has focused on serotonin and produced serotonin-uptake inhibitors, this new drug, developed by Johnson & Johnson, Esketamine contains the active ingredients of ketamine, used to start and maintain anesthesia.  In that role it produces a somewhat trance-like state with accompanying relief of pain and memory loss.  It also ironically has been used as a recreational drug.

Esketamine is in the form of a nasal spray, but there are already clinics administering ketamine intravenously at about $3,000 a crack.  If the FDA approves the use of Esketamine its use would be covered by insurers.

The drawback here for me, as I stress in my memoir Examined Lives which details the rise of the popularity of the lobotomy, is that there is little research on this therapy.  Anecdotally, we know that it has worked for some, but we only have a small sample of cases. And, as in the case of the older drugs, we do not know why it does work when it does.  I hope that if the FDA approves its use that the drug will be well-studied, not just about its short-term efficacy, but about the all important long-term effects.




The active ingredients of ketamine, a popular club drug, show promise in battling deep despair.

The new drug is a nasal spray that delivers the active ingredients of ketamine, widely used as an anesthetic.CreditTeresa Crawford/Associated Press

In a move that may clear the way for the first new treatment in years for depression, an expert panel recommended on Tuesday that federal regulators approve a nasal spray that delivers the active ingredients of ketamine, a popular club drug in the 1980s and 1990s.

The new drug, called Esketamine and developed by Johnson & Johnson, is aimed at people with severe depression, particularly those with suicidal thinking. The panel, with 17 voting members, including psychiatrists and consumer representatives, was nearly unanimous in deciding that the drug’s benefits outweighed its risks. The Food and Drug Administration typically follows the recommendations of its expert panels.

In recent years, scores of clinics have opened around the country, offering to administer intravenous ketamine for depression, on a schedule similar to that of electroshock therapy: as a series of treatments, over a period of days or weeks, and sometimes including follow-up or “booster” visits months later. These treatments, at an average cost of $3,000, are officially “off-label,” and usually are not covered by insurance. Their effectiveness is not well studied, although people who have received the course of treatment have reported rapid, if not always lasting, relief.

If approved, Esketamine would be covered by most insurers.

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The interest in ketamine as a potential treatment dates back to 2006, when researchers at the National Institute of Mental Health, led by Dr. Carlos A. Zarate, reported that 18 people who received the drugs intravenously reported that their despair lifted within hours. The drugs currently on the market for depression typically take two weeks or more to provide any noticeable relief, if they do so at all.

The discovery of ketamine’s effects on depression was serendipitous; the underlying biology of the disorder remains unknown. Some researchers have since turned away from investigating serotonin — the brain transmitter on which most popular antidepressants work — to instead study the effect of ketamine on brain chemistry, to see if the drug provides any clues to the biology of depression.

The federal agency has until March 4 to decide whether to approve the drug.

Brook Johnson, 38, a piano teacher in Westminster, Md., has been waiting on approval for months. Ms. Johnson, who is married and has a 9-year-old daughter, doesn’t know if Esketamine will help her, but said that existing antidepressants have failed. She said she had been in and out of psychiatric hospitals six times and has attempted suicide twice.

“It was back and forth, and then I’d relapse and they’d put me back in,” Ms. Johnson said in an interview last month. “None of the medicines ever seemed to work. At best, they would either numb me out completely, and you just feel nothing and you can’t think.”




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