Book Review: Addiction Noir

 
The Next Right Thing by Dan Barden

To date, I’ve only reviewed one novel here at Addiction Inbox—Steve Earle’s I’ll Never Get Out of This World Alive, featuring the ghost of Hank Williams standing in for the addictive pleasures that musicians are heir to. Now comes The Next Right Thing by Dan Barden, an exemplar of a new literary genre I am going to call addiction noir. Dial Press, the Random House imprint that published the book, is putting Barden forward as a recovering alcoholic who has grokked this scene from the inside. “Dan Barden knows firsthand the difficulties of sobriety…. The Next Right Thing is a powerful new take on the recovery narrative.”

“I’m a recovering alcoholic,” Barden said in the press release, “and I had always wanted to write something about that experience but I couldn’t find a way to tell that story that didn’t seem stupid.”

That changed one morning while Barden was reading the New York Times. “It occurred to me that I could put everything I knew about recovery into a crime story…. There are a lot of great novels about the disease of addiction itself but not so many about recovery, mostly because there’s something very oblique and mysterious about recovery.”

The elements of Barden’s novel certainly aren’t new—a knowing, seen-it-all reformed alcoholic who happens to be an ex-cop, for starters—and plenty of unsavory bad guys. Add in the requisite women, attractive and troubled, or, as our hero Randy Chalmers prefers them, “insane and beautiful.” Chalmers is looking into the suspicious heroin overdose of his AA sponsor, Terry, in a rundown Santa Ana motel, fifteen years sober at the time of his death. The investigation leads Chalmers, sober himself for 8 years, into a tangle of recovery houses fronting as marijuana grow sites and secret shooting sets for amateur porn videos. The crisp quips and one-liners are often focused on the world of addiction. There are nice set pieces, and Chandleresque observations:

--“Those were the days of crack pipes and precious little eating. Even after she got her bearings back, she moved with the anxious, staticky jerks of a cartoon cat. She radiated disease.”

--“I hit him without thinking… but I was surprised to be once again acting without my own consent. That’s the way people talk about taking a drink, as though it’s happening to someone else at some gauzy distance. Like your arm is lifting the glass, and your consciousness has nothing to do with it.”

--“Even with all the step work and therapy and success, people still imagine they will be okay when the are rich. Or married. Or have a baby. Life for an alcoholic is often a process of discovering all the things that don’t make any difference.”

However, the book is marred by the kind of bewildering rumination that can result when a soap opera full of characters is at full boil: “Something about the recovery house scheme didn’t sit right with me. And why was this Simon Busansky character missing in action? Why had Mutt Kelly parked outside my house? Who had made that call to Cathy? Who was the business partner who so preoccupied Terry during the birth of the child he’d always wanted?”

Nevertheless, the book reads quickly, like a noirish mystery should. For influences, Barden lists the usual suspects—Raymond Chandler, Elmore Leonard, Robert B. Parker, George Pelecanos. With decent sales, I could see this becoming a book series, with our sober ex-cop getting himself involved in helping the wrong addict, or helping acquit the right one. With the public recognition of addiction seemingly at an all-time high, and with the ranks of the recently recovered always in the process of being replenished, there just might be a market for this sort of thing.

In a press release, Barden said the book was about “people who are trying to live sober lives against all odds. And what that’s like for me and my friends is complicated and beautiful and dramatic and terrifying. What’s it like to try to do the right thing by your family and friends when many of your instincts run against that?”

Or, as Randy Chalmers puts it: “Here’s another thing you learn in A.A.: when the drunk loses the woman he loves, you know you’re not at the end of the story. You know it’s going to get much worse.”

Photo credit: http://www.danbarden.com

Interview with Dr. Bankole Johnson of the University of Virginia

Tailoring addiction medicine to fit the disease.

(The “Five-Question Interview” series.)

25 years ago, when Dr. Bankole Johnson first began giving lectures about addiction and neurotransmitters in the brain, he had a hard time getting a hearing. That’s because 25 years ago, everybody knew what addiction was: a lack of “moral willpower.” Or, at best, some sort of psychological “impulse control” disorder.  

As a neuropharmacologist by training, and currently professor and chairman of the University of Virginia’s Department of Psychiatry and Neurobehavioral Sciences, Dr. Johnson thought otherwise, and went on make a name for himself by discovering that topiramate, a seizure drug that boosts levels of the neurotransmitter GABA, could be used in the treatment of alcoholism. “I just wasn’t a hospital-type doctor,” he once said. “I was for more intersted in research than clinical practice.” Johnson’s work was featured in the 2007 HBO series, "Addiction."

Born in Nigeria, Dr. Johnson attended the University of Oxford and received his medical degree in Glasgow, Scotland in 1982. At the time, medical understanding of addiction was poor to nonexistent. “Everything we knew—really knew—probably could be written on the back of a postage stamp,” he recalled.

Since then, Dr. Johnson has published numerous articles on psychopharmacology and addiction, and has served on several National Institutes of Health committees and panels. (See my earlier POST on Johnson’s study of drugs for addiction in the American Journal of Psychiatry.)


1. You’re a native of Nigeria. How did you first become interested in medicine?

Bankole Johnson: My father was a doctor and encouraged me. Back then, I had little interest in medicine and was more interested in the arts and perhaps going to law School, for which I had been promised a scholarship.

2. Addiction is called a “disease of the brain,” in Alan Leshner’s famous phrase, but it is still a hugely controversial subject. Are innate biological differences the cause of addiction?

Johnson: Addiction is a brain disease. The roots of the disease lie in brain abnormalities, and these are exacerbated when a vulnerable person uses alcohol excessively or takes illicit drugs.

3. How did you discover that topiramate helped some alcoholics drink less?

Johnson: It was an idea that developed from a hypothesis I came up with based on brain neurochemistry. The central idea was to alter the signals of dopamine, a critical path for the expression of rewarding behavior, through two different and opposite systems—glutamate and GABA.

4. That work led to Topamax for alcoholism, and your more recent work with ondansetron, another GABA antagonist. But what role do environmental and sociocultural factors play in the development of addiction?

Johnson: The environment interacts with genes and brain chemistry to govern behavior. But in the end, it is the changes in the brain that ultimately direct alcohol and drug taking behavior.  The environment therefore provides the context and tuning of the neurochemical signals in the brain.

5. Some people find the notion of addiction as a progressive and incurable condition a hard pill to swallow, so to speak. Why has effective medical treatment for addiction been so slow to develop, and why hasn’t talk therapy been more effective?

Johnson: Talk therapy has some effectiveness, but alone it is not a comprehensive or robust treatment. Progress in the last two decades has been quite rapid. With growing and clear acceptance of the neurobiological underpinnings of addiction, the next decade should herald even more exciting discoveries.  For example, our work on pharmacogenetics promises to provide effective medications—such as ondansetron—that we can deliver to an individual likely to be a high responder, based on his or her genetic make up.

Photo Credit: Luca DiCecco

PROMETA Postmortem

How the latest miracle cure for addiction failed to deliver.

PROMETA™: Last seen going down fast, smoke pouring from all engines.

As reported here at Addiction Inbox, a double-blind placebo-controlled evaluation of PROMETA™ by W. Ling and associates, published online last month in the journal Addiction, found that the much-publicized treatment protocol for meth addiction “appears to be no more effective than placebo in reducing methamphetamine use, retaining patients in treatment or reducing methamphetamine craving.” The authors of the journal paper didn’t accuse Hythiam, the company that makes and sells the product, of not telling the truth. They just said that the treatment didn’t work. The study authors did, however, find evidence of “potential financial conflicts of interests among its advocates…”

An earlier CBS News "60 Minutes" news report in 2009 had raised similar questions, but generated a great deal of publicity for PROMETA™. And the only testing available, a small open study from Texas, had shown positive results. Testimonials began mounting, and a few prominent doctors in the addiction field lent their names to the marketing effort. More conservative voices, like Richard Rawson and the University of Pennsylvania’s Tom McClellan, warned that there was insufficient scientific evidence to push forward with the new treatment—but their concerns were swept aside amid the general enthusiasm for a long-sought antidote to the ravages of methamphetamine addiction.

So how did it happen? And what, if anything, does it teach us about the enterprise of addiction research and treatment?

An editorial by Dr. Keith Humphreys of the Stanford University Medical Centers, which  accompanied the report of the clinical trial in Addiction, attempted to analyze the saga of how “a former junk bond trader with no medical background raised $150 million in capital to market a combination of three medications (gabapentin, flumazenil and hydroxyzine) as a treatment for methamphetamine addiction.” Bear in mind that only one of the drugs—gabapentin—had ever been involved in clinical trials against addiction, with decidedly mixed results. As for the other ingredients, a prominent neuroscientist who blogs pseudonymously as Neuroskeptic, commented at the time: “What the hell kind of a cocktail is that? Gabapentin—OK, it might reduce anxiety and stabilize mood, although the evidence is poor and if you wanted to do that, there are better drugs. Ditto for hydroxazine. And why you want both of those is unclear. But flumazenil? That doesn't do much if you haven't taken a benzodiazepine. But if it did do anything it would be to antagonize the gabapentin.”

All in all, not a promising analysis.

The three drugs are approved for various uses by the FDA, and there is the rub: Off-label practices allow physicians to prescribe medications for uses other than those listed on the official package insert. As useful as this practice can be, it creates a situation in which a “combination of previously approved medications can be marketed without review as a new treatment protocol, despite the fact that none of the individual medications had any evidence nor were originally approved as a treatment for the condition the new protocol targets.”

Under this directive, Hythiam was free to promote the combination of approved medications as a new addiction treatment advance without any significant testing, Humphreys contends.

If the treatment, in the end, proved to be no better than placebo for meth addiction, what made it seem like such a successful new thing under the sun at the outset? Wishful thinking, Humphreys believes: “Many serious, good-hearted people will be shocked at Ling’s negative results because they believed sincerely… we must not yield to our powerful collective desire to believe before we have hard evidence of effectiveness from disinterested, respected sources. The simpler, faster and more miraculous-seeming the cure, the greater should be our skepticism.”

Furthermore: "As was the case with another would-be ‘miracle cure’—ultra-rapid opiate-detoxification—a manufacturer was able to market an untested treatment protocol to addicted patients…”

Why? Because “off-label use of medications is well-established in medical practice and has significant value in many cases, but a balance must be struck with the risk this creates for evasion of the normal safety and efficacy checks by creators of new treatment protocols."

"We have a huge advantage at this historical moment which was not available to people in prior eras who could not determine whether ‘Dr. Keeley’s Double Chloride of Gold Injections’, ‘Dr. Revaly’s Guaranteed Remedy for the Tobacco Habit’ and ‘Dr. Meeker’s Addiction Antidote’ were effective,” writes Humphreys. Namely, “a well-developed addiction treatment research enterprise." And because of that, we should “point with pride to Ling et.al.’s work as an example of how high-quality science can inform suffering people about what will help them and what will not; and those who set public research budgets need look no further for an example of return on investment.”

HUMPHREYS, K. (2012). What can we learn from the failure of yet another ‘miracle cure’ for addiction? Addiction, 107 (2), 237-239 DOI: 10.1111/j.1360-0443.2011.03652.x

Photo Credit: http://blog.nebraskahistory.org

The Future of Addiction Treatment

Is there some way out of here?

Addictions are chronic diseases. They may require a lifetime of treatment. After a number of severe episodes of alcohol or drug abuse, the brain may be organically primed for more of the same. Long-term treatment is sometimes, if not always, the most effective way out of this dilemma. (The same is true of unipolar depression.)

We will need to learn a lot more about chemicals—the ones we ingest, and the ones that are produced and stored naturally in our bodies—if we plan to make any serious moves toward more effective treatment. What we have learned about the nature of pleasure and reward is a strong start. The guiding insight behind most of the work is that addiction to different drugs involves reward and pleasure mechanisms common to them all. The effects of the drug—whether it makes you sleepy, stimulated, happy, talkative, or delusional—constitute a secondary phenomenon. A good deal of earlier research was directed at teasing out the customized peculiarities of one drug of abuse compared to another. Now most addiction scientists agree that receptor alterations in response to the artificial stimulation produced by the drugs are the biochemical key, and that recovery occurs when the brain’s remarkable “plastic” abilities go to work at the molecular level, re-regulating and adjusting to the new, drug-free or drug-reduced status quo. An addict beats addiction by ceasing the constant and artificial manipulation of neuronal receptors, to be entirely unromantic for a moment about the nature of recovery.

But in order for that to happen most effectively, you have to stop taking the drugs.

Comparing our reservoir of pleasure chemicals to money in the bank, Dr. George Koob, Chairman of the Committee On The Neurobiology Of Addictive Disorders at the Scripps Institute in La Jolla, California, draws the following analogy:

We can expend that money over the course of a single weekend’s binge on cocaine or we can expend it over a two-week period in the normal pleasures of everyday life. If you spend these pleasure neurochemicals in one lump sum such as a crack binge, you use up your supply of pleasure for a certain period, and so you pay for it later.

Addicts vividly demonstrate a compulsive need to use alcohol and other drugs despite the worst kinds of consequences—arrest, illness, injury, overdose. What kind of euphoria could be worth such psychic pain? Even stranger, why continue when the drug no longers works as well as it once did due to tolerance? What makes these people eat their words, shred their best intentions, break their promises, and starting using or drinking again and again?

There really is no cheating in this game. The system has to self-regulate. Craving and drug-seeking behavior, once set in motion, disrupt an individual’s normal “motivational hierarchy.” How does this motivational express train come about? It happens at the point where casual experimentation is replaced by the pharmacological dictates of active addiction. It happens when the impulse to try it with your friends transforms itself into the drug-hungry monkey on your back.

 Formal medical treatment and intervention can work, but the results are inconsistent and often little better than no formal treatment at all. Most alcoholics and smokers and other drug addicts, it is frequently asserted, become abstinent on their own, going through detoxification, withdrawal, and subsequent cravings without benefit of any formal programs. Our health policy should not only encourage addicts to heal themselves, but must also help equip them with the medical tools they need in treatment. After all, behavioral habits as relatively harmless as nail biting can be all but impossible to break.

 As detailed by Dr. Mary Jeanne Kreek, a professor and senior attending physician at the Laboratory of the Biology of Addictive Diseases at Rockefeller University:

Toxicity, destruction of previously formed synapses, formation of new synapses, enhancement or reduction of cognition and the development of specific memories of the drug of abuse, which are coupled with the conditioned cues for enhancing relapse to drug use, all have a role in addiction. And each of these provides numerous potential targets for pharmacotherapies for the future.

In other words, when an addiction has been active for a sustained period, the first-line treatment of the future is likely to come in the form of a pill. New addiction treatments will come—and in many cases already do come—in the form of drugs to treat drug addiction. Every day, addicts are quitting drugs and alcohol by availing themselves of pharmaceutical treatments that did not exist twenty years ago. Sometimes medications work, and we all need to reacquaint ourselves with that notion. As more of the biological substrate is teased out, the search for effective medications narrows along more fruitful avenues. This is the most promising, and, without doubt, the most controversial development in the history of addiction treatment.

Fighting fire with fire is not without risk, of course. None of this is meant to deny the usefulness of talk therapy as an adjunct to treatment.  However, consider the risks involved in not finding more effective medical treatments. Better addiction treatment is, by almost any measure, a cost-effective proposition.

Photo: http://www.manorhouserehab.com/

“When Did I Become the Junkie Auntie Mame?”

Courtney Love tells her tangled tale in a new e-book.

Maer Roshan, author of Courtney Comes Clean: The High Life and Dark Depths of Music’s Most Controversial Icon, logged a dozen “exhilarating and exhausting” sessions with the widow of Nirvana’s Kurt Cobain over the course of a year, pulling together a definitive look at Love’s drug addictions and other demons. Roshan taped countless hours of interviews, and received additional written material from the “Tolstoy of texting,” as Love refers to herself. The book is highly readable, almost, one is tempted to say, addictively so. Sure, it’s tabloid stuff—let he or she who has never peeked at Gawker or Jezebel cast the first stone.

Roshan, who has performed editorial duties at Radar, New York, Talk, and Interview, does his best to shape the former rock star’s rambling tales into a coherent narrative. (Disclosure: I have contributed articles and blog posts to Roshan’s online addiction and recovery magazine, The Fix.) But coherence is an uphill struggle with Love, who is clearly a highly intelligent, strong-willed woman; an addict who suffers from comorbid mental disorders, including such possibilities as bipolar disorder, borderline personality disorder, and narcissistic personality disorder. Her brief acting career and string of dramatic financial ups and downs, in the grand tradition of Hollywood stars and superstar musicians dragged down by fame, fate, and drugs, has led to her current “florid obsessions” with financial conspiracies against her, Roshan writes. 

At times she has installed a “sobriety minder” in her New York townhouse; at other times she has tried to bash a Vanity Fair reporter over the head with an Oscar snatched from Quentin Tarantino.  None of this would be of anything but passing interest except for the Keith Richards-style Queen of Drugs role that she has either assumed or has had thrust up on her. As she told Roshan: “Kim Stewart called me up screaming, ‘Courtney, what are we going to do? Kelly [Osbourne] is passed out and is blue on the floor!’ She wasn’t doing too okay back then. For some reason, Kim also called me when Paris Hilton got pulled over for her last DUI. And Lindsay Lohan called me after she was arrested…. And then Lindsay’s father called me for advice every day for weeks. It was weird. I mean, I’m not even friendly with these girls. When did I become the junkie Auntie Mame?”

So, is she a sober or an addicted Auntie Mame? Is she the go-to girl for straight talk on drugs and sobriety, or just another enabler? She has been through formal rehab perhaps a dozen times now. At one point in the book, she crows about the fact that all the drugs she’s currently taking are “entirely legal,” then flies to a posh London Hotel, using a personal physician and a 24-hour nursing staff to kick her addiction to Adderall—prescription speed. Love appears to have the “chronic relapsing” part of addiction down pat.

Roshan notes that, “like many addicts, she has found herself increasingly isolated and withdrawn in recent years.”

 I asked Maer Roshan a few questions about the book, to which he kindly responded:

Q. Has this woman every really been clean and sober for an extended period, or is she just conning everybody about her recovery?

Maer Roshan: She's certainly not sober in any way that would pass muster at A.A., but she's come a long way from the demons that plagued her past… She admits to using prescription pills. (She makes a point to note that they're all legally prescribed.) She also enjoys a few drinks now and again. But she's nothing like the addict she was five years ago, when she was shooting smack five times a day or holed up in her house in L.A, watching for police cars and smoking kilos of crack. For someone like Courtney, that's real progress. In light of all the damage that drugs have inflicted on her life and her family, I think she is serious about sobriety. She's seen first-hand the damage that drugs can do. After all, they killed her husband and ruined her relationship with her daughter. But ultimately sobriety means different things to different people. As they say in A.A., it’s about progress rather than perfection, so even though she's far from a teetotaler, her progress is impressive.

Q. Lindsay and Paris and all the young drug people make pilgrimages to her for advice. Is that a good thing or a bad thing?

Roshan: I think it's neither a good thing nor a bad thing. Obviously, Lindsay or Paris would probably get better advice from a person more grounded in sobriety, or from a therapist or doctor. But, as she notes in the interview, being famous does strange things to people's heads, especially famous women, so in a way it's understandable that younger girls in the same position would relate to her. Believe it or not, Courtney's actually pretty shrill on the subject of drugs. She’s been known to reach out to those women, even if they don't reach out to her.

Q. Courtney seems obviously co-morbid. Has she ever sought psychiatric help?

Roshan: Obviously I'm not qualified to diagnose her. I know she's seen a fair share of psychiatrists throughout her life. In my book, her mother notes that Courtney was agitated and anxious from the time she was a toddler. Her parents built her a special hut attached to their main house in New Zealand, in part to keep her from attacking her brothers and sisters. She was prescribed Valium from the time she was seven. Like most crazy people, she has the capacity to be brilliant and funny and extremely entertaining. But she's also filed with bitterness and unbelievable rage, and you never quite know which Courtney you're gonna get. She's a blast to hang out with, but as I can attest from personal experience, it's kind of scary when her rage is directed at you.
------------

So what to make of her? “Most people think I dry out at these really posh places,” she told Roshan, “but I’ve landed in some pretty gnarly spots.” And that’s when I began to feel some sympathy for Love, seeing her falsehoods and contradictions and obsessions in the light of her addictions, known that there must have been plenty of horrifying nights, and equally agonizing mornings, and self-loathing, and a lot of time surrounded by people, but always alone. What to make of her? I don’t think we know yet. I hope she gets better, stronger, wiser, and ends up making a fool out of me.

Photo Credit: http://blogs.sfweekly.com

Army Doctor Sees Victory, and a Dangerous Drug Bites the Dust—Almost.

An interview with the man who blew the whistle on the neurotoxic malaria drug in the U.S. Army’s kit bag.

A dangerous malaria drug invented by the Army and commonly used by soldiers and civilians alike causes everything from episodes of psychotic violence to nightmares more real than reality, and is finally being withdrawn as the first-line treatment for troops in malarial zones.

Lariam, known medically as mefloquine, has also been a licensed treatment for civilians abroad for more than 25 years. Yet it has only been in the recent past that common knowledge of Lariam’s dangers has surfaced publically.

The development of Lariam was a prime example of military-industrial cooperation. Discovered at the Walter Reed Army Institute of Research during the Vietnam war, initially tested on prisoners at the Joliet Correctional Center in Illinois, and marketed worldwide by Hoffmann-La Roche, mefloquine was an urgent response to high malaria rates in U.S. combat troops overseas. Unfortunately, such close cooperation also led to a lack of adequate clinical testing—the practice that underpins the notion of drug safety. Ashley M. Croft of the Royal Army Medical Corps in Britain has written that in the case of Lariam, “the first randomized controlled trial of the drug in a mixed population of general travellers was not reported until 2001.” Croft believes the FDA was influenced by “the powerful military-industrial-governmental lobby into over-hasty decisions.”

In addition, “travel medicine experts in most countries were slow to recognize the danger signals associated with Lariam…. As late as 2005 a reviewer in the New England Journal of Medicine, also an employee of the US military for over 20 years, continued to maintain… that Lariam was a ‘well tolerated’ drug,” according to Croft. The victims of all this pharmacological hoodoo, Croft maintains, “have been those many business travellers, embassy staff, tourists, aid workers, missionaries, soldiers and others who were well at the start of their journeys into malaria-endemic areas…”

Largely due to the efforts of Dr. Remington Nevin, a medical epidemiologist and a physician in the U.S. Army, who went public about Lariam’s potential for causing psychological illness, military officials announced in December that the Army was done with Lariam as a first-line malaria preventative except for “special circumstances.” In the past, such special circumstances have allegedly included its use as an interrogation drug at Guantanemo.

As far back as 2004, an alarming number of suicides among troops in Iraq prompted calls for an investigation of Lariam. “The military is ignoring this drug’s known side effects,” Steve Robinson of the National Gulf War Resource Center told UPI. In October of 2004, Sen. Dianne Feinstein (D-Calif) urged then-Secretary of Defense Donald Rumsfeld to investigate the drug: “Given the mounting concerns about Lariam as expressed by civilians, service members and medical experts about its known serious side effects, I strongly urge you to reassess,” she wrote to Rumsfeld. Meanwhile, Mark Benjamin and Dan Olmsted of UPI were reporting that “mounting evidence suggests Lariam has triggered mental problems so severe that in a small percentage of users it has led to suicide. UPI also reported that soldiers involved in a string of murder-suicides at Fort Bragg, N.C., in the summer of 2002 after returning from Afghanistan had taken the drug.”

Almost ten years later, Sen. Feinstein wrote another letter, this one to Secretary of Defense Leon Panetta, complaining that a 2009 policy limiting the use of mefloquine among U.S. troops was not being followed. Although parent company Roche discontinued Lariam in the U.S., generic versions remain available, and the company continues to sell Lariam in other countries. “My office has been contacted recently by servicemembers who were prescribed mefloquine when one of the other medications would have been appropriate and were not given the FDA information card. These servicemembers are now suffering from preventable neurological side effects,” including  balance problems, vertigo, and psychotic behavior,” she wrote.

In addition, as a military medical instructor told Addiction Inbox: “Some service members might ‘double up’ on their weekly dose, or increase the frequency of dosing, intentionally for recreational purposes. There is no evidence that the military educates service members to avoid this temptation or that it is unsafe. Users might even justify it by believing it could enhance the drug's anti-malarial activity. In the military, it is frequently a tenet of our culture that ‘if one is good, two is better.’"

In November,  military officials overseas stopped almost all use of mefloquine in malaria-prone areas in Africa and the Middle East. Army Col. Carol Labadie, the service’s pharmacy program manager, commented on the long overdue change: “If that means changing from one drug to another because now this original drug has shown to be potentially harmful… it is in our interests to make that change.”

As Croft wrote, it was not a case of inconvenient research being deliberately witheld. Rather, “the necessary pre-licensing research was simply never carried out.”

Questions still remain about the use of mefloquine at Guantanamo as an “enhanced interrogation technique.” Last year, Stars and Stripes ran an investigation of the matter and concluded: “Medical experts say the Defense Department policy of giving detainees large doses of mefloquine is poor medical practice at best and torture at worst.”

INTERVIEW WITH DR. REMINGTON NEVIN

—Is there any good science behind the notion that mefloquine might be addictive?

Dr. Remington Nevin: I am speaking to you in an individual capacity, and my opinions are my own and in no way reflect those of the U.S. Army or the Defense Department. There is no evidence that mefloquine is addictive per se, but the drug is well-known to produce vivid, technicolor dreams, and as a result it is frequently viewed as an incidental and convenient form of recreation among people, including Peace Corps volunteers and military service members, who find themselves already required to take the drug, and otherwise typically without access to alternative drugs of abuse, such as alcohol. The vivid "rock star" fantasies frequently reported are often perceived as consolation for the isolation and loneliness that typical accompany travel to remote areas where mefloquine is prescribed.

Ann Patchett, a prize-winning author, recently wrote a book called State of Wonder in which mefloquine features prominently, and her writing was likely based to a good degree on her and her acquaintances' experiences with the drug. Patchett herself actually refers to the drug's "recreational" properties and alludes in a recent interview to her having wanted to "take the drug out for a spin" (see http://thedianerehmshow.org/)

REHM: Did you take Lariam when you went to the Amazon?
PATCHETT: I did, I did. And actually, if I hadn't gone to the Amazon, I probably would've just taken it recreationally at home because I really wanted to take it out...
REHM: Experience it.
PATCHETT:...for a spin, right.
REHM: Yeah.
PATCHETT: And the side effects of Lariam listed on the package, psychotic dreams, terrible nightmares, paranoia, suicide is a possible side effect and I've known a lot of people who have had true psychosis on Lariam.

—Can you lay out what you know about mefloquine causing hallucinatory and dissociative effects in travelers who take it for malaria?

Dr. Nevin: [The symptoms] closely mimic those of a condition known as anti-NMDA receptor encephalitis, which an expert in the field, Dr. Dalmau, describes as including "anxiety, fear, bizarre or stereotypical behaviour, insomnia, and memory deficits". It is thought that rising levels of antibody to the NMDA receptor induces… widespread downstream dysregulation of  limbic dopaminergic and noradrenergic tone, which ultimately are responsible for producing the syndrome's psychotic effects… This limbic dysregulation may also be similar to what is seen with the chemical NMDA receptor antagonists, including ketamine and phencyclidine, which share with mefloquine a particular propensity towards impulsivity and dissociation. For these reasons I conclude that mefloquine should be characterized as a dissociative hallucinogen.

—What is a dissociative hallucinogen?

Dr. Nevin: It is this property that also likely explains the drug's association with suicidality and acts of violence. Mefloquine is the only non-psychotropic drug listed among the top ten associated with acts of violence, and there is a growing literature linking it causally to suicide.  It may be that the combination of mefloquine-induced amnesia, dissociation, and hallucinations (many with vivid religious or persecutory themes) creates a perfect storm that can trigger impulsive acts of violence. It is not uncommon for those recovering from (and surviving) mefloquine psychosis to report engaging in suicidal gestures that in retrospect were devoid of any fear of consequences…. Just within the past year, in a paper in the journal Science, Bissiere and colleagues demonstrated mefloquine interfering with context fear response in the hippocampus.


—Could you expand on the notion of "vivid rock star fantasies" experienced by some users?

Dr. Nevin: Extremely vivid dreams are among the most widely reported "adverse effect" of the drug. Users can frequently describe their dreams in great detail even well into the next day and, in some cases, the dreams seem to take on an almost lucid quality. Many experience gratifying and deeply pleasurable dreams that they almost don't wish to awaken from; conversely, for some others, the effect seems to be quite the opposite, with the reported nightmares being particularly haunting the next day.

—You have referred to Lariam as a "zombie" drug. Could you expand on that?

Dr. Nevin: If you must know, the reporter for AP caught me on Halloween, but I believe the term is quite apropos. The drug is the pharmaceutical equivalent of the living dead; it is somehow able to survive controversies that would have quickly killed other drugs. Interestingly, Lariam has been quietly delisted although generics remain widely available. To further stretch the metaphor, the drug is also decidedly neurotoxic and kills brain cells; one can say it "eats brains", and lastly, I would argue that a "zombie-like" state is not an unreasonable description of the most extreme adverse effects of the drug.

—I'm shocked to discover mefloquine on the list of top 10 drugs associated with acts of violence. Could you comment on a non-psychoactive drug making that list?

Dr. Nevin: It is quite shocking. Mefloquine isn't typically considered a psychotropic drug, but it probably should be recharacterized as a psychotropic medication with incidental anti-malarial properties. Of the drug contained in a 250mg tablet, only about 1-2mg, less than 1%, is ultimately found at the site of its intended anti-malarial activity, in the circulation. And although the neuropharmacokinetics are still somewhat unclear, arguably a far greater percentage of the drug is ultimately found in brain tissue than in the circulation. Incredibly, when the drug was undergoing FDA licensing, this brain penetration wasn't even well-characterized. Transcripts from the licensing meetings clearly show committee members skipping over this fact without much consideration. Certainly there seems to have been no requirement to submit the drug to neurotoxicity testing, despite many related quinoline compounds having demonstrated well-characterized, permanent neurotoxicity at least 40 years earlier.


—How common is the use of mefloquine in the U.S. as a whole?

Dr. Nevin: There has been a fairly rapid decline in the use the drug, correlating with rising appreciation of mefloquine's dangers and awareness of contraindications to its safe use. Malarone is now the predominant anti-malarial prescribed within a large network of U.S. travel clinics. The U.S. military, which developed the drug just over 40 years ago, recently prohibited the use of mefloquine as first-line agent, and has dramatically curtailed its use after research revealed the drug had been widely prescribed to service members with mental health contraindications. Recently, the U.S. Centers for Disease Control further clarified guidance against routine use of mefloquine in service members, conceding that use of mefloquine may "confound the diagnosis and management of posttraumatic stress disorder and traumatic brain injury".

—What are the consequences of mixing Lariam with alcohol?

Dr. Nevin: There is fairly good evidence from case reports that alcohol may potentiate the deleterious effects of mefloquine, but the mechanism remains controversial. It had been suspected that alcohol simply exerted an inhibitory effect on mefloquine metabolism, but now… it seems likely that alcohol exerts a direct pharmacodynamic effect.


—Lariam is still sometimes prescribed for children traveling in malaria zones. Are there special dangers for kids?

Dr. Nevin: As the popularity of the drug is declining among adults, some experts with ties to industry have been peddling the drug for niche pediatric use, ostensibly because it is well tolerated. Unfortunately, such claims are based on studies which in many cases are deeply flawed and…. even verbally fluent but younger children may not have the experience or perspective to properly describe these symptoms. Apart from these considerations, I would argue that I don't think enough is understood about the neurophysiological effects of the drug to justify its use even in older children and adolescents.  Mefloquine is a psychotropic drug. Given what we are learning of mefloquine's effects on the limbic system, even at relatively low doses, it seems at least plausible that the developing brain might in some way be adversely affected by the drug, particularly during long-term dosing.

—Why was the Army so slow to move on mefloquine?

Dr. Nevin: To put things in perspective, understand that mefloquine is the sole product of an aggressive 20-year, multi-million dollar effort by the U.S. Army. Mefloquine was identified only in the early 1970s after tens of thousands of other quinoline compounds had failed toxicity and efficacy tests. By the time of mefloquine's U.S. licensure in 1989, it was essentially DoD's last and only hope. So, if I could rephrase your question, if mefloquine is as safe as the Army once claimed, then why is it no longer the drug of choice? If we assume that this quiet policy change was made in tacit acknowledge of safety concerns, then the question is, precisely what new information has informed this decision, why has this change taken so long to occur, and most importantly, what harm might this policy change now be seeking to avoid, which may already have accrued among those in whom the drug had been previously used?  

The reasons for the Army's silence on these questions are likely quite banal. Admitting mefloquine is a dangerous drug would be a bitter pill for any Army medical leader to swallow. Many of today's senior medical leaders were intimately involved in the studies that saw the drug rise to prominence, and many are on record over the previous decades publicly defending the drug against the increasingly validated claims of its earlier critics. Absent external pressure to do so, it is likely of little benefit for these senior medical leaders to suffer the humiliation that would come from admitting what they might now otherwise privately concede. Saying nothing is the path of least resistance on their journey to a comfortable retirement.

—Could you comment on allegations of Lariam use as an interrogation drug at Guantanamo?

Dr. Nevin: The use of mefloquine at Guantanamo represents either medical malpractice with culpability at some of the highest levels of military medical leadership, or it suggests something far more intentional and sinister. I typically believe that one should never ascribe to malice what can be attributed to simple incompetence, but in this case, I am not so certain. There are too many inconsistencies and unanswered questions. The issue will ultimately require the release of medical records, open hearings, and testimony to resolve. I am confident this will happen.

Book Review: Writers On The Edge

A compendium of tough prose and poetry about addiction.

Here’s a book I’m delighted to promote unabashedly. I even wrote a jacket blurb for it. I called it an “honest, unflinching book about addiction from a tough group of talented writers. These hard-hitters know whereof they speak, and the language in which they speak can be shocking to the uninitiated—naked prose and poetry about potentially fatal cravings the flesh is heir to—drugs, booze, cutting, overeating, depression, suicide. Not everybody makes it through. Writers On The Edge is about dependency, and the toll it takes, on the guilty and the innocent alike.”

I am happy to stand by that statement, content to note that this collection of prose and poetry on the subject of addiction and dependency by 22 talented writers, with an introduction by Jerry Stahl of “Permanent Midnight” junky fame, includes a number of names familiar to me. That makes it all the easier to recommend this book—I know some of the talent. Take James Brown, a professor in the M.F.A program at Cal State San Bernardino, the book’s co-editor, who offers an excerpt from his excellent memoir, This River.  James is no stranger to the subject, having pulled out of a drug and alcohol-fueled nosedive that would have felled lesser mortals for good. “Even though you’ll always be struggling with your addiction, and may wind up back in rehab,” Brown writes, “at least for now, if only for this day, you are free of the miracle potions, powders and pills. If only for this day, you are not among the walking dead.” Or my friend Anna David, who is an editor at The Fix, an online addiction and recovery magazine to which I frequently contribute, and author of several books, including Party Girl and Falling for Me. Anna poignantly recalls “my shock over the power than booze had… it was the greatest discovery of my life.” And Ruth Fowler, another Fix contributor and author of Girl Undressed, delivers up a brilliantly detached story of her life as an addict on both coasts and just about everywhere else, which begins with the line, “I gravitated to the fucked up writers.”

Then there are the contributors I don’t know but wish I did, like co-editor Diana Raab, a registered nurse and award-winning poet, as well as co-author of Writers and Their Notebooks, who offers a poem to her grandmother: “Your ashen face and blond bob/disheveled upon white sheets/on the stretcher held by paramedics/lightly grasping each end, and tiptoeing.” Or another poet, B. H. Fairchild, author of the marvelous collection, Early Occult Memory Systems of the Lower Midwest: “When I would go into bars in those days/the hard round faces would turn/to speak something like loneliness/but deeper, the rain spilling into gutters/or the sound of a car pulling away/in a moment of sleeplessness just before dawn.”

And more: Frederick Barthelme, author of Double Down: Reflections on Gambling and Loss. Stephen Jay Schwartz, best-selling crime novelist  and former director of development for filmmaker Wolfgang Petersen. Writers Rachel Yoder, Victoria Patterson, David Huddle, and Scott Russell Sanders. Etc. This collection is a rich brew of essay, poetry, and memoir. A tough book, a brutal book, a real heartbreaker with grit. Some people get stronger and rise; some don’t. It is a thoughtful and creative compendium of addiction stories, and some of them will surprise you. All of them are solidly written, laid out with an unrelenting realism.

Here it is, these authors are saying. This is how it plays out. Unforgettable stuff.