10/30/15

Seasons of Temptation

“Watch and pray that you may not enter into temptation. The spirit indeed is willing, but the flesh is weak.” (Matthew 26:41)

John Owen oriented his book, Of Temptation around his thoughts on the above verse. Chapter six of that work looks at what Owen called the seasons of temptation. He observed how there were various times or seasons when temptation is commonly at hand. These opportunities will unavoidably “seize upon the soul” unless we are watchful to prevent it. When we are under such a season, Owen cautions us to be particularly on our guard so that we do not enter or fall into the power of temptation.

The first of these seasons occurs in a time of outward prosperity. “Prosperity and temptation go together.” Prosperity is the ground for many temptations and without eminent supplies of grace it will create the opportunity for any one of a myriad of temptations. Then it will provide all the food and fuel the temptation needs to burn hotter and brighter.

In Proverbs 1:32 it says the prosperity or complacency of fools destroys them. It hardens them in their way and makes them despise instruction. It puts the day of reckoning far off, lest its terror should influence you into changing your ways. “Without a special assistance, it hath an inconceivably malignant influence on believers themselves.” Agur prayed that he would not have riches (Proverbs 30:8, 9) so that he would not forget the Lord.

David was confident that he would not be moved in his prosperity (Proverbs 30:6), but he gravely overestimated himself. Although Solomon said we should rejoice in the day of prosperity (Ecclesiastes 7:14), Owen advised us to rejoice in the God of mercies, who does good for us by his patience and forebearance despite our unworthiness. He urged that we consider how evil lies close at hand in prosperity. “A man in that state is in the midst of snares. Satan hath many advantages against him; he forgeth darts out of all his enjoyments; and, if he watch not, he will be entangled before he is aware.”

You need something to give poise or stability to your heart. Formality in religious practice can creep in, laying the soul open to various temptation in their full power and strength. “Satisfaction and delight in creature-comforts, the poison of the soul, will be apt to grow upon thee.” Owen said to be vigilant and careful in such a time or you will be surprised. There is a hardness and disregard of spirituality that can happen in prosperity. Many people’s disregard of this warning has cost them dear. “Blessed is he that feareth always, but especially in a time of prosperity.”

Another season to watch for is when there is a time of neglect in our communion with God, a formality in our religious duty, a time of “the slumber of grace.” A soul in such a state of mind should wake up and look around. Their enemy is close at hand and they are about to fall into a condition that could cost them dear for the rest of their life. While a time of neglect in your communion with God is bad enough, it is also an indication that something worse is at the door. Recall how Peter fell into a time of spiritual and physical drowsiness and did not heed the caution of Christ to “watch and pray” so that he not enter into temptation. And since he was not watching as he should, he entered into it.

Consider, then, O poor soul, thy state and condition! Doth thy light burn dim? Or though it give to others as great a blaze as formerly, yet thou seest not so clearly the face of God in Christ by it as thou hast done? Is thy zeal cold? Or if it do the same works as formerly, yet thy heart is not warmed with the love of God and to God in them as formerly, but only thou proceedest in the course thou hast been in? Art thou negligent in the duties of praying or hearing? Or if thou dost observe them, thou doest it not with that life and vigour as formerly? Dost thou flag in thy profession? . . . If thou art drowsing in such a condition as this, take heed; thou art falling into some woeful temptation that will break all thy bones, and give thee wounds that shall stick by thee all the days of thy life. Yea, when thou awakest, thou wilt find that it hath indeed laid hold of thee already, though thou perceivedst it not; it hath smitten and wounded thee, though thou hast not complained nor sought for relief or healing.

Perversely, a season of great spiritual enjoyment is often turned into a season of danger and temptation because of Satan and the weakness of our hearts. Consider Paul, who in 2 Corinthians 12:1 related having visions and revelations of the Lord. Yet to keep him from becoming conceited because of the greatness of the revelations, yet he was given a thorn in the flesh to keep him from becoming conceited (2 Corinthians 12:7). Satan sees that being possessed by the joy before us, we become lax over many of the ways of approach to our souls. So he seeks and finds some advantage to use against us. “Let us not say, ‘We shall never be moved;’ we know not how soon God may hide his face, or a messenger from Satan may buffet us.”

A fourth season of temptation is with self-confidence. At times of high self-confidence temptation is usually close at hand. The case of Peter is a clear example of this. He said he would not fall away or deny Jesus. Even if all the others fell away, even if it meant his death he would stand fast (Mark 14:29-31). “This said the poor man when he stood on the very brink of that temptation that cost him in the issue such bitter tears.” Within a few hours of his confident declaration that he would never deny Christ he did so three times.

Would you think that Peter, who had walked on water with Christ, who confessed him to be the Son of God, who was with him on the mount, would at the questioning of a servant girl—when there was not legal inquisition or process against him—would swear that he did not know who Jesus was? So if you would guard against sin, beware of self-confidence.

And this is the first thing in our watching, to consider well the seasons wherein temptation usually makes its approaches to the soul, and be armed against them.

Here is a link to Overcoming Sin and Temptation, a trilogy of three works by Owen: “Of the Mortification of Sin in Believers;” “Of Temptation;” and “Indwelling Sin.”

10/28/15

Positively NOT Psychiatry

Positive psychiatry is a growing phenomenon within the profession of psychiatry. And Dr. Dilip Jeste, a former APA President, seems to be the primary “evangelist” for the positive psychiatry movement. The theme for his year as APA President in 2012 was: “Pursuing Wellness Across the Lifespan.” He said positive psychiatry was the future of psychiatry. In a Psychiatric News article for June of 2012, Jeste said: “I believe that, as the medical field begins to appreciate the value of positive psychosocial factors in the prevention and management of pathology, positive psychiatry will increasingly take a central stage within medicine and health care.”

David Rettew, a child psychiatrist, wrote of his invitation by Dr. Jeste, to speak at a symposium on Positive Psychiatry at the 2015 annual conference of the American Psychiatric Association (APA) held in Toronto. He was excited by the opportunity and sees positive psychiatry as an opportunity for his profession to become “physician experts in mental health,” as opposed to their current emphasis on mental illness. Dr. Rettew noted that for too long, psychiatry has had two primary interventions: psychotherapy and medications. “Expanding our efforts into domains of wellness gives us so many more avenues to help children and families thrive.”

Jeste is also one of the editors of Positive Psychiatry: A Clinical Handbook, which was just released in June of 2015. Dr. Rettew is one of the contributing authors to that work. Jeste, Barton Palmer (co-editor of Positive Psychiatry), Rettnew, and Samantha Boardman (contributor to Positive Psychiatry) coauthored an article in the June 2015 issue of the Journal of Clinical Psychiatry, “Positive Psychiatry: Its Time Has Come.” They noted how psychiatry has traditionally focused on the diagnosis and treatment of mental illnesses. However, trying to find what causes mental illness and developing “safe and effective treatments” has not been enough to fulfill “the enormous potential of psychiatry to promote human welfare.”

The time has come to integrate positive mental health into psychiatric practice, training, and research and to expand psychiatric expertise to encompass the full spectrum of mental functioning.

Instead of an emphasis on managing mental disorders, Jeste et al. said positive psychiatry is a science and clinical practice that seeks to promote well-being through “assessment and interventions aimed at enhancing behavioral and mental wellness.” As a branch of medicine, positive psychiatry is rooted in biology and seeks to decipher the biological underpinnings of positive psychosocial characteristics (PPCs). “And eventually promote health and well-being through psychosocial/behavioral and biological interventions.“

Positive psychiatry traces its immediate influence to the positive psychology movement that was pioneered by Milton Seligman in the later 1990s. In his presidential address to the American Psychological Association in 1998, he called for “a reoriented science that emphasizes the understanding and building of the most positive qualities of an individual.” These qualities include: optimism, courage, work ethic, future-mindedness, interpersonal skills, the capacity for pleasure and insight, and social responsibility. Similarly, Jeste et al. pointed to how a growing body of research shows that higher levels of PPCs, such as resilience, optimism, and social engagement are associated with objectively measured better health outcomes. You can watch a TED talk given by Seligman, “The New Era of Positive Psychology,” where he describes positive psychology.

Possible biomarkers for positive mental health were noted by Jeste et al. They were: allostatic load, telomere length, oxidative stress, neuroinflammation and immune function. The authors then ran through the “association” of several positive psychological characteristics (PPCs) with biological factors. Jeste et al. believed that by strengthening the development of positive traits through psychotherapeutic, behavioral, social and biological interventions, “positive psychiatry has the potential to improve health outcomes and reduce morbidity as well as mortality.”

Instead of being narrowly defined as a medical subspecialty restricted to the management of mental illnesses, psychiatry of the future will develop into a core component of the overall health care system. Psychiatrists will thereby more explicitly reclaim their role as physicians in addition to their roles as mental health professionals. Clearly, much more work is needed to make positive psychiatry a norm in psychiatric practice, but it is time to start that process.

I’m troubled by the rhetoric of the so-called “positive psychiatry” movement. On the one hand, it is encouraging to hear an eminent psychiatrist like Dr. Jeste call for attention and research into positive psychological traits. Psychiatry has concentrated on the prevention and management of pathology, while it largely ignored positive psychological traits like resilience, optimism and self-efficacy and how important they are in preventing and managing pathology. This next quote, taken from the Jeste et al. article, succinctly captures both what encourages me and sends chills up my spine: “The time has come to integrate positive mental health into psychiatric practice, training, and research and to expand psychiatric expertise to encompass the full spectrum of mental functioning.”

The time has come to consider positive mental health in psychiatry. However, the expansion of psychiatric “expertise” and the authority that will accompany such expertise in modern society is not a positive outcome for society. It has disturbing social and political dimensions that were foreseen and noted by psychiatrist Thomas Szasz over fifty years ago. In his 1977 work, The Theology of Medicine, he said:

In the scientific-technological concept of the state, therapy is only a means, not an end: the goal of the therapeutic state is universal health, or a least unfailing relief from suffering. The untroubled condition of man and society is a quintessential feature the medical-therapeutic perspective on politics: conflict among individuals, and especially the individual and the state, is invariably seen as a symptom of illness or psychopathology; and the primary function of the state is accordingly the removal of such conflict through appropriate therapy—imposed by force if necessary. (Thomas Szasz, The Theology of Medicine, p. 128)

If we value personal freedom and dignity, we should, in confronting the moral dilemmas of biology, genetics, and medicine, insist that the expert’s allegiance to the agents and values he serves be made explicit and that power inherent in his specialized knowledge and skill not be accepted as justification for his exercising specific controls over those lacking such knowledge and skill. (Thomas Szasz, The Theology of Medicine, p. 17)

It seems that within “positive psychiatry,” psychiatrists are seeking to not only maintain their hegemony over preventing and managing pathology, but expand it to “encompass the full spectrum of mental functioning.” There has been a growing concern with the failed promises of psychiatry, such as the identification of biological or genetic cause in the “mental illness.” Critiques of DSM diagnosis have come from within psychiatry from individuals such as Allen Frances and Thomas Insel. Frances was the chair for the DSM-IV. Insel is the Director of the National Institute of Mental Health (NIMH). In Saving Normal, Frances’s critique of the DSM-5 and the medicalization of everyday life, he said: “Unfortunately, the DSM approach has been far too influential—dominating the field in a way we never intended.” Insel announced before the publication of the DSM-5 that the NIMH would be “reorienting its research away from DSM categories” (see “Psychiatry Has No Clothes”).

It was encouraging to hear Dr. Rettew acknowledge how psychiatry has been having an identity crisis. He alluded to the dominance psychiatry had as “skilled therapists” when it was ruled by psychoanalytic thought. But there is another way to see the consequences of the “explosion of neuroscience” and the “promise of medications.” Just as the reliability and validity of psychiatric diagnosis was effectively questioned, and from within and outside psychiatry, and psychiatrists faced losing their social status and power, they reframed diagnosis along purely biological guidelines and aligned themselves with the pharmaceutical industry.

As Rettew said: “Recent research has revealed that many of the risks of medications may have been under appreciated while the benefits somewhat overblown.” He noted how neuroscience research has been impressive, but lacking immediate clinical applications. Despite the promise that these results may eventually help improve early identification and facilitate effective treatment with a variety of disorders, “in reality there remains a large number of dots to connect before that actually happens.”

Positive psychiatry seems to be about maintaining hegemony in the face of another serious challenge to its authority. It is not humbly admitting the limitations of a purely biochemical explanation for human behavior, it’s just “kicking the can” of research further down the road. The reductionism of the medical model is still at the heart of how positive psychiatry views psychopathology. Biology is still the “root” of positive psychiatry. Jeste et al. said:

As a branch of medicine, positive psychiatry is rooted in biology and seeks to decipher biological underpinnings of PPCs [positive psychosocial characteristics] and eventually promote health and well-being through psychosocial/behavioral and biological interventions.

Jeffery Liebeman, the president of the APA immediately after Dr. Jeste, has published a book, Shrinks, that purports to tell the story of how psychiatry overcame its dubious past. Lieberman seems more willing to acknowledge the still dominant medical model in psychiatric diagnosis and treatment. With regard to the field of psychiatry, he said: “Ever since the very earliest psychiatrists began conceiving of disturbed behaviors as illnesses (and even long before), they held out hope that direct manipulation of a patient’s brain might one day prove therapeutic” (Shrinks: The Untold Story of Psychiatry, p. 160). With regard to diagnosis, he said: “The DSM-III turned psychiatry away from the task of curing social ills and refocused it on the medical treatment of severe mental illnesses.” (Shrinks, p. 147)

Research into the impact of positive psychological characteristics on mental functioning and psychopathology is certainly a good thing, but it is positively NOT psychiatry that should have a controlling, leading role in that research. Its seemingly positive and hopeful view of the future is based upon seeing humanity as biological machines. While I don’t think this would lead to the dystopian future, like that portrayed in the Terminator movies, the rise of the biological machine would be just as apocalyptic. For an alternative way of doing psychiatry, see “Psychiatry Is Not Neurology.”

10/26/15

Doubling Up Your Drinking

Would you like to be able to double the amount of alcohol that enters into your bloodstream when you drink? Let’s say you consume the equivalent of two standard drinks containing one ounce of alcohol. Your blood alcohol level (BAL) would double and you would likely exceed the legal driving limits in thirty minutes. Oh, and you would feel drunker as well. Does this sound crazy? Yet that is exactly what happens to someone who has had gastric bypass surgery.

A recent 2015 study, “Effect of Roux-en-Y Gastric Bypass Surgery,” published in JAMA Surgery evaluated the physical and subjective effects of ingested alcohol on individuals who had received a common from of gastric bypass surgery called Roux-en-Y gastric bypass. The find is from a small study of 8 obese women who had undergone the surgery and 9 obese women who had not yet had the surgery. All the women consumed the equivalent of two standard alcoholic drinks or two placebo nonalcoholic drinks in two 10-minute drinking sessions.

HealthDay reported that the researchers measured the blood alcohol concentration (BAC) levels of the participants. “Drunkenness” was measured by matching each participant’s behavior to an “Addiction Research Center Inventory.” BAC levels rose much faster in the bypass group and peaked at levels twice those seen in the non-bypass group. The BAC levels of the bypass group also exceeded legal driving limits for thirty minutes after consuming their second drink. “BAC levels never exceeded legal driving limits among the non-bypass group.”

Feelings of drunkenness were also greater in the bypass group. Using criteria developed by the U.S. National Institute on Alcohol Abuse and Alcoholism, the researchers concluded that just two drinks were the equivalent of a binge-drinking episode with the potential risk of an alcohol use disorder. Dr. Samuel Klein, one of the study’s authors, said:

This surgery literally doubles the amount of alcohol that immediately enters your bloodstream. . . . And it also increases the patient’s long-term risk for alcoholism, because the risk for a binge episode of drinking goes up. And we know that binge drinking increases the risk for going on to develop alcoholism in the future.

Although Klein and his team used a more rigorous methodology than had been used before, the study’s finding isn’t new. Dr. John Morton, chief of bariatric and minimally invasive surgery at the Stanford University School of Medicine, said this was a well-known phenomenon. “It’s about physiology,” he said. There is an increased sensitivity to alcohol because the surgery removes alcohol receptors in the stomach. These receptors are also found in the liver. “And if you bypass and remove a portion of either of these, you have a change in blood alcohol levels.”

ScienceLine reported on a woman who lost 180 pounds within a year of her gastric bypass surgery in 2009. She started ordering wine in place of dessert at dinner so she wouldn’t sit there ‘”twiddling my fork” while others ate their dessert. The occasional glass of wine became more often and she spent the next two years fighting an alcohol use disorder. She began drinking at home alone, two bottles of wine per occasion. She began hiding bottles from her husband, driving while drunk and blacking out when drinking. She discovered injuries she didn’t remember getting.

A 2012 study, “Prevalence of Alcohol Use Disorders Before and After Bariatric Surgery,” found that while alcohol use disorder (AUD) symptoms were not significantly different one year after the surgery, they were significantly higher in the second postoperative year. The presence of an AUD in the year before surgery substantially increased the odds of an AUD in the first two postoperative years. “Regular alcohol consumption prior to surgery also independently increased the likelihood of postoperative AUD.” One in 8 participants reported consuming at least three drinks per typical drinking day; and 1 in 6 participant said they drank at a hazardous level in the second postoperative year.

A 2013 Swedish study, “Alcohol Consumption and Alcohol Problems After Bariatric Surgery” did a long-term follow up of over 2,00 obese patients who had three types of bariatric surgery: vertical banded gastroplasty (VBG), banding and gastric bypass. The follow up time of the study ranged from 8 to 22 years. Alcohol consumption standards established by the World Health Organization (WHO) were used to assess the risk levels of alcohol consumption during the follow up period.

During the follow up time, 93.1% of the surgery patients and 96.0% of the controls reported alcohol consumption classified as low risk by the WHO. However, in comparison to the control group, the gastric bypass group had an increased risk of alcohol abuse diagnoses, alcohol consumption at least at the WHO medium risk level, and related alcohol problems. VBG also increased the risk of these conditions, while banding was not different from controls.

Another 2013 study, “Substance Use Following Bariatric Weight Loss Surgery,” looked at the course of substance use (alcohol, cigarettes, recreational drugs, and composite substance use), as measured by the Compulsive Behaviors Questionnaire. Participants completed questionnaires preoperatively and 1,3, 6, 12 and 24 months after surgery. There were no significant changes in participant’s reported frequencies of cigarette smoking or recreational drug use. However, there was a significant increase in alcohol use for participants who had undergone RYGB surgery, the same Roux-en-Y gastric bypass as reported above in the 2015 study by .

Because patients have a reduced tolerance for alcohol after RYGB surgery, they may experience the rewarding aspects of alcohol use sooner and more frequently, which may contribute to the increase in frequency of alcohol use after LRYGB surgery.

Steph Yin for ScienceLine noted that many patients are unaware of the risk of an alcohol use disorder when they get gastric bypass surgery. And scientists aren’t clear themselves on why the risk exists. An early theory was that of addiction transfer. People adopt new addictions after weight-loss surgery because they can no longer fulfill their food addictions. However, evidence like that above in “Effect of Roux-en-Y Gastric Bypass Surgery” suggests there may be an anatomical explanation. Namely that metabolic and hormonal changes triggered by gastric bypass leave patients particularly vulnerable to alcohol use disorders. It’s possible, said Yin, that both are right. Or maybe it’s something else entirely. We just don’t know at this point.

According to James Mitchell, a doctor and professor of neuroscience at the University of North Dakota, “Whether it’s addiction transfer or something else going on, we really don’t know at this point.” What is certain is that the high rates of alcohol use disorders in postoperative gastric bypass patients cannot be attributed to chance.

10/23/15

Fatal Consequences with Anger

Beginning in Matthew 5:21, Jesus encourages his audience to strive to obey the spirit of a commandment and not just a strict literal interpretation of it. That is the significance of the repeated formula here, “You have heard it said … But I say to you.” Here Jesus unpacks the deeper implications of one of the ten commandments, you shall not murder. The same should be understood with the remaining commandments or sayings in Matthew 5:21-48. Leon Morris, in his commentary on Matthew said:

Jesus is protesting against a strictly literal interpretation of the commands, an interpretation that indicates an apparent willingness to obey what God has said, but which imposes a strict limit on obedience and leaves scope for a good deal of ungodly behavior. He is laying down authoritatively how these commands of God should be understood.

You have heard that it was said to those of old, ‘You shall not murder; and whoever murders will be liable to judgment.’ But I say to you that everyone who is angry with his brother will be liable to judgment; whoever insults his brother will be liable to the council; and whoever says, ‘You fool!’ will be liable to the hell of fire. (Matthew 5:21-22).

The sixth commandment in Exodus 20:13 simply said: “You shall not murder.” But here there is the addition of: “and whoever murders will be liable to judgment,” which spells out the consequence to someone who committed murder. His audience would be thinking, “Well, of course there should be judgment against a murderer!” Then Jesus extends the agreement that there should be judgment against a murderer to apply to lesser forms of hostile behavior towards others. He says anyone who is angry with another person, who insults someone—who even calls them a fool—will be liable to “hell-fire and damnation.”

The valley of Hinnom, was a ravine just south of Jerusalem, had been the place where worshipers would burn their children as a sacrifice to Molech (2 Kings 23:10). In Jeremiah, there was a prophecy of judgment against this place (Jeremiah 7:31-32); and it came to be linked with the final place of torment. Leon Morris commented that in Jewish tradition, it was believed the Last Judgment would take place in the valley of Hinnom. The implication for us in Matthew is that anger and insults toward another will be judged alongside murder at the Last Judgment.

It would be wrong to say the passage equates anger and insults with murder. Rather, Jesus teaches here that these behaviors are also sinful and deserving of judgment. Just as murder self-evidently warrants judgment against the murderer, don’t minimize or rationalize your angry and insulting behavior. To illustrate his point, Jesus then gave two examples where unresolved anger or resentment has consequences.

So if you are offering your gift at the altar and there remember that your brother has something against you, leave your gift there before the altar and go. First be reconciled to your brother, and then come and offer your gift. Come to terms quickly with your accuser while you are going with him to court, lest your accuser hand you over to the judge, and the judge to the guard, and you be put in prison. Truly, I say to you, you will never get out until you have paid the last penny. (Matthew 5:23-26)

In effect Jesus is saying, get your priorities straight! “The act of sacrifice is not as important as the spirit in which it is done.” Unresolved resentment nullifies any religious sacrifice you bring to God. Just as it is wise to settle a dispute out of court and not risk the possibility of a judgment against you, the time to reconcile with someone you have wronged is before the dispute escalates to the point of formal judgment. Anger, insults and resentments are just as deserving of judgment before God as murder. The standard is to be willing to “live peaceably with all,” if it is within your power to do so (Romans 12:18).

Self-control and resolution of anger and resentment in recovery is a fundamental necessity. In the chapter “How It Works” in the A.A. Big Book, Bill W. wrote: “Resentment is the ‘number one’ offender. . . . If we want to live, we have to be free of anger.” Bill wrote that resentment destroys more alcoholics than anything else. “From it stem all forms of spiritual disease.” One of the ways of addressing anger and resentment is to list them in completing the “searching and fearless moral inventory” of a Fourth Step. “We asked ourselves why we were angry.”

It is plain that a life which includes deep resentment leads only to futility and unhappiness. To the precise extent that we permit these, do we squander the hours that might have been worthwhile. But with the alcoholic, whose hope is the maintenance and growth of a spiritual experience, this business of resentment is infinitely grave. We found that it is fatal. For when harboring such feelings we shut ourselves off from the sunlight of the Spirit. The insanity of alcohol returns and we drink again. And with us, to drink is to die.

In the “Step Ten” essay in Twelve Steps and Twelve Traditions, Bill wrote: “It is a spiritual axiom, that every time we are disturbed, no matter what the cause, there is something wrong with us.” His audience was other members of Alcoholics Anonymous, but the truth of what he said applies to all people. In counseling, I regularly show others how in anger or resentment, we literally or metaphorically point an accusing finger at another person. So do that right—point your finger at someone or something; then look at your hand. While there is one finger pointing out, there are three pointing back at you. Ask yourself why you are angry.

Few people have been more victimized by resentments than have we alcoholics. It mattered little whether our resentments were justified or not. A burst of temper could spoil a day, and a well-nursed grudge could make us miserably ineffective. Nor were we ever skillful in separating justified from unjustified anger. As we saw it, our wrath was always justified. Anger, that occasional luxury of more balanced people, could keep us on an emotional jag indefinitely. These emotional “dry benders” often led straight to the bottle. Other kinds of disturbances—jealousy, envy, self-pity, or hurt pride—did the same thing.

Murder, anger and resentment exist on a continuum of behaviors worthy of judgment before God. The commandment to not murder includes a warning to not hold on to anger or resentment. Twelve Step recovery sees anger and resentment as a form of spiritual disease that cuts off the individual from the sunlight of the Spirit. Unresolved, this spiritual disease leads to drinking and death.

This is part of a series of reflections dedicated to the memory of Audrey Conn, whose questions reminded me of my intention to look at the various ways the Sermon on the Mount applies to Alcoholics Anonymous and recovery. If you’re interested in more, look under the category link “Sermon on the Mount.”

10/21/15

Dirty Little Secret

Quoting Steven Hollon, in his book The Emperor’s New Drugs, Irving Kirsch said it was a “dirty little secret” that there was only a small difference between the experimental and control groups for the patients who participated in the randomized clinical trials (RCTs) used to approve SSRIs. Be sure to get this: the pharmaceutical companies that produced the drugs AND the regulatory agencies that approved them, knew there was essentially no difference between the effects of the drug and the placebo. Yet the drugs were approved for use with humans. “Many have long been unimpressed by the magnitude of the differences observed between treatments and controls, what some of our colleagues refer to as the ‘dirty little secret’ in the pharmaceutical literature.”

Kirsch was originally interested in studying the placebo effect, and not the antidepressant drug effect. “How is it, I wondered, that the belief that one has taken a medication can produce some of the effects of that medication?” He was not surprised to find a substantial placebo effect of the medications on depression. But he was surprised to see how small the drug effect was. “Seventy-five percent of the improvement in the drug group also occurred when people were give dummy pills with no active ingredient in them.”

You can read an article by Kirsch describing the research process described here in: “Antidepressants and the Placebo Effect.”

He replicated the findings in another study published in 2002, using the data submitted to the FDA by the pharmaceutical companies in their process of obtaining approval for six new generation antidepressants. There were some advantages to using the FDA data set. First, they received data on the published and unpublished clinical trials conducted by the pharmaceutical companies. What was particularly important here was that: “The results of the unpublished trials were known only to the drug companies and the FDA, and most of them failed to find a significant benefit of drug over placebo.”

A second advantage was that the FDA trials all used the same primary measure of depression—the Hamilton depression scale (HAM-D). The third advantage was that the FDA data was the same data used for the approval of the medications. So if there had been anything wrong with the trials, one would think, the medications would not have been approved.

In the data sent to us by the FDA, only 43% of the trials showed a statistically significant benefit of drug over placebo. The remaining 57% were failed or negative trials. . . . The results of our analysis indicated that the placebo response was 82% of the response to these antidepressants.

One explanation for Kirsch’s results could be that the replication done in 2002 contained both the published and unpublished clinical trials. The inclusion of failed and negative trials would have lowered the positive results required by the FDA for approval of a medication. So the placebo response was greater in this replication than it was in their original study because of including the unpublished trials. Nevertheless, the majority of the trials failed to show positive results. Remember that the pharmaceutical companies themselves conducted these studies; and that they were the trials done in the process of gaining approval for their medications.

Getting approval of a drug by the FDA requires the submission of two studies showing the new drug is better than a placebo. It doesn’t matter if it takes you ten studies to get those two; only the two positive ones count for approval. The requirement is that two trials have to demonstrate the drug is more effective than a placebo, and that measurement has to be statistically significant. Kirsch’s analysis found just a 1.8-point difference on the HAM-D scale between drug and placebo—a difference that is not clinically significant, even though it may be statistically significant. The National Institute for Health and Clinical Excellence (NICE) has set the criterion for a clinically significant difference between drug and placebo to be at least three points on the HAM-D scale.

A criticism of Kirsch’s 2002 study was that the results were based on clinical trials conducted on subjects who were not very depressed. So Kirsch et al. (2008) reanalyzed the data in: “Initial Severity and Antidepressant Benefits.” They found that “the overall effect of new-generation antidepressant medications is below recommended criteria for clinical significance.” Only for the most extremely depressed patients was there evidence for clinical significance, according to the HAM-D scale. Yet they also concluded this difference was “due to a decrease in the response to placebo rather than an increase in the response to medication.”

So the question becomes, what do all these drugs have in common that gives them a slight, but statistically significant effect on depression over placebo? The answer is that they all produce side effects.

Clinical trials are all double-blind studies, meaning that neither the patient nor the doctor is supposed to know whether the patient is given the active drug or the placebo. Yet in one study, 80% of patients guessed correctly whether or not they were on the drug or placebo; and 87% of doctors also guessed correctly. So most patients and most doctors could break the blind by guessing according to the presence or absence of side effects to the medications. Additionally, “89% of the patients in the drug group correctly ‘guessed’ that they had been given the real antidepressant, a result that is very unlikely to be due to chance.”

So clinical trials are not really double blind studies if most patients can guess whether or not they have been given the real drug rather than the placebo. This ability to “break blind” has been known in the research literature since 1986 when Rabkin et al. published their study, “How Blind is Blind” in the September issue of Psychiatry Research. Yet drug trials continue to use inert placebos.

But what would happen if an active placebo were used in clinical trials? Active placebos have been used with antidepressants in other studies. See “Active Placebos Versus Antidepressants for Depression.” Moncrieff et al. reported that: “differences between antidepressants and active placebos were small.” Kirsch noted that in the nine clinical trials discussed by Moncrieff et al. where an active placebo (atropine) was used, there was only a significant difference in two of the studies.

In the vast majority (78 percent) of the clinical trials in which active placebos were used, no significant differences were found between the drug and the placebo. So comparisons with inactive placebos are much more likely to show drug-placebo differences than comparisons with active placebos. This suggests that at least part of the difference that has been found between antidepressant and placebo may be due to the experience of more side effects on the active drug than on the placebo.

It’s good this dirty little secret is becoming more widely known. But unfortunately the horse has already left the barn. Too bad it wasn’t getting press fifteen years ago before the SSRIs started going off-patent. The pharmaceutical companies have already gouged the public with their SSRI profits and their drugs have gone generic.

Eli Liliy’s Prozac went off patent in 2001. GlaxoSmithKline’s Paxil has been off-patent since 2003. Forest Labs’ Celexa patent expired in 2003. Pfizer’s Zoloft patent expired in 2006. Wyeth’s Effexor (now marketed by Pfizer) went off-patent in 2006. Wellbutrin, developed by Burroughs Wellcome and later acquired by GlaxoSmithKline, lost its patent in 2006. Lexapro was developed by Forest Laboratories in conjunction with Lundbeck and they won two patent extensions. But it lost exclusivity in 2012.

10/19/15

Binge Drinking Biomarkers

Over two years ago, the Chair of the DSM-5, David Kuyper admitted that despite telling patients for decades that they anticipated finding biomarkers for psychiatric disorders, that discovery continues to be “disappointingly” out of reach. The hope is that at some future time, the promise will become a reality. “In the future, we hope to be able to identify disorders using biological and genetic markers that provide precise diagnoses that can be delivered with complete reliability and validity.”

In “What are Biomarkers?”, Strimbu and Tavel said by definition, biomarkers are objective, quantifiable characteristics of biological processes. The WHO said a biomarker is almost any measurement that reflects the interaction between a biological system and a potential hazard. “The measured response may be functional and physiological, biochemical at the cellular level, or a molecular interaction.” They cautioned that the overreliance on biomarkers “presents a serious and persistent risk of producing misleading, and in some cases dangerous, erroneous conclusions.” And yet, in many areas of research, it appears this warning is ignored. Keep this in mind as we review here three different studies into biomarkers for—of all things—binge drinking.

A recent press release announced that a biomarker distinguishing binger drinkers from moderate drinkers among young adults has been found by researchers at the University of Illinois at Chicago. The press release suggested the biomarker, “called phosphatidyl ethanol (PEth), could be used to screen young adults for harmful or heavy drinking such as binge drinking.” The lead author for the study, Mariann Piano, said: “Using a biomarker of heavy alcohol consumption such as PEth along with self-reporting could provide an objective measure for use in research, screening and treatment of hazardous alcohol use among young adults.” But I’m not convinced that it would be an appropriate or even helpful screening tool as suggested.

The association of PEth to alcohol consumption has been known for some time, so the suggestion this was a “groundbreaking” research study examining “the relationship between biomarkers and alcohol consumption” by Brent McCluskey in The Fix was a bit misleading. McClusky later clarified that the study was “groundbreaking” because this was the first study to investigate PEth levels in young adults. A search of just the journal Alcohol and Alcoholism, where the Piano et al. study was published, indicated there were 34 total articles meeting the search criteria of “PEth.”

Dr. Lena Gustavsson was the winner of the ESBRA Award in 1994 for her work on phosphatidyl ethanol (PEth). Aradottir et al. reported in 2006 that PEth was a promising new marker for ethanol abuse. They found that blood concentrations of PEth were highly correlated to alcohol intake. “Its diagnostic sensitivity is higher than that for previously established alcohol markers.”

In 2011, Isaksson et al. noted that since the formation of PEth was specifically dependent upon ethanol, “the diagnostic specificity of PEth as an alcohol biomarker is theoretically 100%.” They added that the half-life of PEth in blood is around four days.

Helender et al. (2012) concluded that PEth was the most sensitive biomarker of current alcohol consumption and prior drinking because the PEth test can detect lower consumption levels.

Jain et al. in 2014 found strong associations between PEth and self-reported measures of alcohol consumption among young injection drug users. They suggested PEth may be a useful marker “in settings where alcohol consumption is difficult to assess,” or to confirm or refute self-reported measures of alcohol consumption.

Kechagias et al. (2015) concluded that PEth was the only marker that could discriminate between abstinence and a moderate daily consumption of alcohol.

So the PEth biomarker would help to confirm whether or not someone is honestly reporting their recent consumption of alcohol. It would NOT be a biomarker to identify at risk binge drinkers. And it seems to have little application for treatment other than as an “honesty test” in treatment to affirm or rule out recent alcohol consumption. It may be a more accurate or sensitive test than a breathalyzer, but that doesn’t strike me as groundbreaking news.

Biological Psychiatry had another study in its in June 2015 issue by Warnault et al. that suggested a gene variant, Met68BDNF, reduced the release of brain-derived neurotrophic factor (BDNF) in mice. These mice would consume excessive amounts of alcohol and continue to drink despite negative consequences. An NIH news release said the researchers treated the alcohol with bitter-tasting quinine. “This suggests Met68BDNF carriers compulsively drink alcohol despite aversive consequences.”

The implication is that in humans, this gene variant may put an individual at greater risk of developing an alcohol use disorder. By administering a pharmaceutical compound developed to mimic the action of BDNF, the researchers were able to stop the compulsive drinking behavior in the mice. “This compound (LM22A-4) may have potential as a therapeutic for humans. It appears to reduce compulsive drinking without a generalized effect on motivation.”

BDNF is a protein in humans that is encoded by the BDNF gene. It acts on certain neurons, “helping to support the survival of existing neurons, and encourage the growth and differentiation of new neurons and synapses.” In the brain, it is active in areas vital to memory, learning and higher thinking. The BDNF gene may play a role in the regulation of stress response and in the biology of mood disorders. The expression of BDNF is reduced in Alzheimer’s and Huntingdon disease. Linda Gabriel described BDNF as Miracle-Gro for the brain.” If you’re interested, Alomone Labs is offering a free sample of human BDNF.

Although an interesting finding, it has only been demonstrated within mice at this point in time. If further research were to show that Met68BDNF in humans was associated with a higher risk of alcohol use disorders, compounds like LM22A-4 may help in reducing the neurochemical element in craving or compulsive drinking. But there’s more to compulsive drinking than just biology and neurochemistry.

The most interesting study to me was reported in News & Views for The Scripps Research Institute. Herman et al. reported that the deletion of GIRK3 subunits (G-protein-gated inwardly rectifying potassium) in mice. They compared “knockout” mice, ones missing GIRK3, with normal mice. During a simulated “happy hour” when access to alcohol was limited to two hours a day, GIRK3 knockout mice consumed significantly more alcohol than the control group of normal mice. When mice were given continuous access to alcohol, conditions where mice do not get intoxicated, the effect was not evident.

There was no difference found between the GIRK3 and control mice in how alcohol was metabolized. Both groups also experienced a similar loss of balance, sleepiness and reduced body temperature in response to alcohol. The researchers thought there were two possibilities. Mice without GIRK3 could be drinking more because they felt more pleasure from alcohol, so they wanted to drink more. Or they felt less pleasure and thus needed to drink more to reach the same level of pleasure as normal mice.

In order to answer this question, they looked at the mesocorticolimbic dopaminergic pathway (the reward pathway in the brain) and found that the pathway was completely insensitive to alcohol without GIRK3. Even at high doses, alcohol did not alter the firing of neurons missing GIRK3. Alcohol also failed to trigger the release of dopamine in the ventral striatum of GIRK3 mice. The results suggested that mice drink more alcohol to boost the engagement of other neural pathways mediating alcohol’s rewarding effects.

By reintroducing GIRK3 in the knockout mice, the researchers were able to alter the binge drinking down to normal levels. Normal mice with increased GIRK3 drank even less. “This has led the researchers to believe that a compound selectively targeting GIRK3-containing channels may hold promise for reducing alcohol consumption in heavy binge drinkers.” An abstract for the study published in the Proceedings of the National Academy of Sciences can be found here.

PEth, BDNF, and GIRK3 are all biomarkers of some sort that are being applied to the potential hazard of “binge drinking.” As Strimbu and Tavel observed, the key issue is determining the relationship between any given biomarker and the relevant clinical endpoints, which in this case is binge drinking. In some cases, biomarkers may be shown to measure the process of a key pathway stage in reaching the clinical endpoint of binge drinking. But assuming this relationship risks mistaking correlation for causation. PEth seems to be an example of a correlational biomarker. And caution needs to be exercised at this point with any conclusions drawn from the findings of studies with BDNF and GIRK3.

While there is growing evidence of a genetic connection with alcoholism, the evidence is not conclusive at this time. Following Carleton Erickson, I’d say that while alcohol dependence runs in families, it is not purely a genetic disease. “Rather, the tendency to become alcoholic is inherited. Thus alcoholism can skip generations, or affect only certain individuals in an alcoholic family.” See “The Genetic Connection” for more discussion on genetic research into alcohol dependence.

10/16/15

Swift as Lightning

Despite the opposition of the most influential resident of the parish, William M’Culloch became the minister at Cambuslang, Scotland on April 29th, 1730. He would remain as the minister of the church in Cambuslang until his death forty years later. M’Culloch was a capable and faithful minister, notable for his learning and piety, but he was not an eloquent preacher. Even his son said his father was not “a very ready speaker.” This lack of eloquence was significant for the “Cambuslang work” in 1742; it could not be attributed to his preaching. You never heard of Cambuslang? George Whitefield looked upon the “Cambuslang work” as the greatest revival he ever witnessed.

About five miles from Glasgow, the size of the Cambuslang parish was roughly 900 by 1742, and it had a long association with evangelical faith. M’Culloch would rise and study from 5 a.m. to 8 p.m., allowing 2 or three hours for relaxation during that time. He also spent some of this time in private prayer. M’Culloch had been preaching on the doctrine of regeneration and newness of life to his congregation for about a year before the initial awakening in February of 1742. A narrative drawn up by M”Culloch in 1742 confirmed this practice.

After the Sunday evening sermon, M’Culloch would read to his congregation from the accounts of the ministry of George Whitefield, Jonathan Edwards and others. A Narrative of Surprising Conversions, by Edwards, was first published in London in 1837. It described the process of Christian conversion and the beginning of the Great Awakening in Northampton Massachusetts. Whitefield’s Journals were first published separately between 1738 and 1741. George Whitefield had been on a preaching tour to America, which was covered in his fifth Journal. You can read a copy of D. MacFarlane’s The Revivals of the Eighteenth Century, which highlights Cambuslang here; and The Journals of George Whitefield here.

So the revival in Cambuslang came to an informed people. They had been reading and hearing about revival in other places, and were prayerfully hoping it would happen with them. For several months before the Cambuslang Awakening, M’Culloch preached to crowded congregations. There was a more than ordinary concern about religion evident among his people. Whitefield himself had preached in Scotland during the summer of 1741, but he had not yet been to Cambuslang.

M’Culloch wrote to Whitefield of the fruit of his work, noting where fifty persons were “savingly converted” through the power of his sermons in the Glasgow area. MacFarlane said that many of those who afterwards who were “brought under the power of the truth” at Cambuslang, spoke of these sermons by Whitefield as among the first means to awaken in them a concern for their salvation. M’Culloch noted the immediate visible fruits were seen in the visible reformation of former sinners. Some individuals who had been known for their swearing and cursing now didn’t. Others who drank to excess were sober. Among the people, there was also a forgiveness of injuries, a making of restitution for harms done, and more.

An air of expectancy increased throughout the parish of Cambuslang as the winter of 1741 progressed. One woman was “much and oft” taken up in praying for a revival of Religion so that she seemed in a great measure to forget herself and her own concerns. Then on February 14th, a Sabbath, it began when a young woman of seventeen, Catherine Jackson, came under extreme conviction and distress, and was escorted from the service. M’Culloch counseled with her for about three hours afterwards. She had several semi-hysterical outbursts, convinced that her sins were too many to be received by Christ.

Catherine was finally calmed in prayer, saying that Christ had told her that He cast all her sins behind her back. There were many other people in the room, including several of her friends and her two sisters. Many of these others were also weeping and crying out. The next few days saw the repeat of similar circumstances of spiritual counseling. That Thursday, February 18th, M’Culloch preached on Jer. 23:6. About fifty men and women sought out the minister afterwards for prayer and conversation.

Afterwards, crowds of people came to Cambuslang. Sermons were provided almost daily. Several of the local ministers assisted M’Culloch in the teaching and exhorting of the ever-growing crowds. Other ministers traveled from distant parts of Scotland to participate in Cambuslang. Afterwards they sent attestations of the genuineness of the work to their own people. Whitefield was among the first to receive the news about Cambuslang. He hoped upon his return to Scotland to see “greater things than ever.” M’Culloch, in a letter to Whitefield at the end of April, said he was still holding daily sermons and longed to see Whitefield at Cambuslang. His hope was soon realized.

On Tuesday, July 6, Whitefield came to Cambuslang, and preached three times: at two, six and nine o’clock. The attendant commotion far outdid all he ever saw in America. The weeping and distress of the people—smitten by the scores—was beyond description. Whitefield likened it to a battlefield, where those struck were carried off and brought into the house like wounded soldiers. Throughout the entire night prayer and praise was still heard in the fields where Whitfield had preached. M’Culloch invited Whitefield to assist at the annual communion service scheduled to occur that weekend.

Whitefield preached to twenty thousand people on Saturday. He also preached on the Sabbath and again on Monday. Each day the crowd was approximately twenty thousand. Whitefield said on Monday, the motion passed “swift as lightning” from one end of the audience to the other. Thousands were bathed in tears; others wringing their hands; some almost swooning; others crying and mourning over a pierced Savior. The communion service was so impressive, that contrary to the church custom of yearly times of communion, Dr. Webster of Edinburgh, proposed that a second one be held soon. A decision was reached by the Cambuslang session of elders to again dispense the sacrament again on August 15th.

The second sacrament saw crowds even greater than at the first; upwards of 30,000 people came. For comparison, the estimated population of the city of Glasgow in 1740 was only 17,034! There were three thousand communicants, and another thousand who could not get tokens. Someone wanting to participate in the communion service but who was from another parish (and thus not known by the presiding minister) would receive a lead token from their own minister. The token represented them as a member in good standing and approved to receive communion by their own minister.

The Sunday worship began at 8:30 in the morning, and the last communion table was being served at sunset. One of the original Marrow Men, John Bonar, then 72, was present as an assisting minister. He was an ancestor of the distinguished Bonars of the eighteenth century: Horatius, John and Andrew. His health was so frail that it took him three days to ride the eighteen miles from his home to Cambuslang. This second communion was the high-water mark of the Cambuslang revival. Whitefield said: “Such a passover has never been heard of.” Whitefield thought it was the greatest revival he had ever witnessed.

The great scandal of religious enthusiasm during the Enlightenment, an Age of Reason, meant that the news about Cambuslang spread like wildfire. There were faintings, outcries, and “bodily agonies.” A nineteen year-old youth couldn’t walk or speak, and scarcely could draw his breath. A woman had pains under spiritual conviction akin to those of childbirth. Another woman frightened her poor husband when she roared out twice in a manner not like a human, after family devotions. She had trembling and a terrible thirst; smelled an odor she associated with the Bottomless Pit. A man said his body was almost taken off from the place where he was. He remained in this state about two hours, then had a vision akin to that of Ezekiel in the valley of dry bones, followed by another of a shower of manna.

Concern over the physical manifestations at Cambuslang raised the fear of the spirit of Quakerism, crypto-Camizards (French Prophets), or other enthusiastic sects. So the “Cambuslang Wark” was disparaged. In a testimony dated April 30, 1751, M’Culloch admitted that in 1742 there were many who fell under various bodily agitations and commotions. He stated that we cannot conclude that such persons were under the influence of the Spirit. These agitations could have been a result of the power of the imagination, or from a bodily disorder. He cautioned that no one should suspect themselves, merely because they had not experienced such effects.

Conversely, we cannot infer that the because of such effects, the cause was not divine. Referring to the crying out during worship, he said it was best to avoid extremes. Hearers should resist the urge if they can (and not disrupt the service). Preachers should not encourage such expressions, nor rebuke them too severely. He noted how God had used such outcries to contribute to the awakening of others. He noted how some who tried to restrain themselves from crying out began bleeding from the mouth and nose, continuing for some time to the injury of their health and the alarm of all nearby. MacFarlan, author of Revivals of the Eighteenth Century, argued that tears, groaning, fainting and even strong bodily agitations should be expected effects to those brought to the conviction of their sin. He suggested that the crowds response at Pentecost was probably similar to that of Cambuslang; the bodily agitations are the natural effects of such feelings as are here expressed.

A true assessment of the reality of a revival is the fruit that it bears, and Cambuslang did have it. One example was evident to visitors of Cambuslang. They were impressed by the warm affection and sense of community found among the residents. Above we noted the changes in the live of sinners: the profane became reverent; the drunkards became sober. However, the telling fruit of any revival is the Christ-likeness of the participants: those who truly love Christ will do as he commands. On April 22, 1751, M’Culloch compiled a list of four hundred awakened in the 1742 revival, who had continued from then until their death, or until 1751 to behave in a good measure “as becometh the gospel.” He had been careful to gather his information by either personal observation, or written and verbal information from persons of established character who knew those of whom they report.

The above experiences at Cambuslang sound much like those associated with the Toronto Blessing of twenty years ago. But we should remember that Cambuslang happened in a time when the experience of high or intense “religious affections” was suspect; perhaps even more so than today. Additionally, they occurred within the context of a Presbyterian communion service. I think the following quote from Thoughts on the Revival, by Jonathan Edwards gives a balanced perspective on the existence and experience of these religious phenomena.

There is a great deal of difference in high and raised affections, which must be distinguished by the observer. Some are much more solid than others. There are many exercises of the affections that are very flashy, and little to be depended on; and oftentimes a great deal appertains to them, or rather is the effect of them. . . . that which sometimes more especially obtains the name of passion, is nothing solid or substantial. But it is false philosophy to suppose this to be the case with all exercises of affection in the soul, or with all great and high affections; and false divinity to suppose that religious affections do not appertain to the substance and essence of Christianity. On the contrary, it seems to me that the very life and soul of all true religion consists in them.

10/14/15

Antipsychotic Big Bang

Duff Wilson wrote in “Side Effects May Include Lawsuits” that antipsychotics were a niche product for decades. Yet they have recently generated sales that have surpassed that of “blockbusters like heart-protective statins.” In the 1990s, pharmaceutical companies began marketing them for much broader uses than the original FDA approved uses for more serious mental illnesses, like schizophrenia and bipolar disorder. A Scientific American article reported that pediatric prescriptions for atypical antipsychotics rose 65%—from 2.9 million to 4.8 million—between 2002 and 2009. And a New York Times article noted that federal investigators have found widespread overuse of psychiatric drugs by older Americans with Alzheimer’s disease.

There are two more facts to introduce you to about neuroleptics or atypical antipsychotics. First, in 2008, antipsychotics sales reached $14.6 billion, making them the biggest selling therapeutic class of drugs in the U.S. Second, each of the following pharmaceutical companies that marketed antipsychotics has been investigated for misleading marketing under the False claims Act. All their neuroleptics—Risperdal (risperidone; Johnson & Johnson), Zyprexa (olanzapine; Eli Lilly), Seroquel (quetiapine; AstraZeneca), Geodon (ziprasidone; Pfizer), and Abilify (aripiprazole; Bristol-Myers Squibb and Otsuka)—are now off patent.

The primary use off-label use of neuroleptics for the elderly and with children has been for behavioral control. A recent study commissioned by the Pennsylvania Department of Human Services found that children between the ages of 6 and 18 who were in foster care was four times higher than other youth in Medicaid. More than half of these youth had a diagnosis of ADHD. “This is concerning, as the majority of these youth did not have another diagnosis that clinically indicated the use of antipsychotics.” Risperidone was the most frequently prescribed antipsychotic medication among the youth. However, Abilify and Seroquel grew to exceed risperodone over the course of the study. Zyprexa was the least commonly used antipsychotic among all youth.

A trade group for nursing homes, The American Health Care Association, indicated that while antipsychotics helped some dementia patients who have hallucinations or delusions, “They also increase the risk of death, falls with fractures, hospitalizations and other complications.” The American Psychiatric Association, among others pointed to a JAMA Psychiatry study that showed mortality risks increased in patients given antipsychotics to reduce their symptoms of dementia. Another study published in Health Policy said the benefits and harms of using antipsychotic medications in nursing homes should be reviewed.

Antipsychotic medication use in nursing home residents was found to have variable efficacy when used off-label with an increased risk of many adverse events, including mortality, hip fractures, thrombotic events, cardiovascular events and hospitalizations.

Another “add on” area for neuroleptic use is when it is used with an antidepressant for “treatment resistant” depression. On BuzzFeed, Cat Ferguson reported how the sale of antipsychotics such as Abilify, and Zyprexa “skyrocketed” as they were approved to treat depression as an add-on medication. Seroquel is not FDA approved to treat major depression, but along with Abilify and Zyprexa is approved to treat bipolar depression in adults. Zyprexa and Seroquel are approved for some indications of bipolar disorder in adolsecents, but Abilify is only used off label with bipolar children, having “low or very low evidence of efficacy.” See the Psychopharmacology Institute for more information on these drugs and their approved and off-label uses.

Ferguson quoted a few psychiatrists expressing concern about the antipsychotic boom, and there are some surprises given other stands they’ve taken. Allen Frances, the former chair for the DSM-IV, agreed there has been heavy marketing of antipsychotics. He thought they are prescribed too quickly for depression and without clear indication of their efficacy. He added there seemed to be pressure from the pharmaceutical companies. He said: “These drugs should have a narrow indication, and instead they’ve become the highest revenue-producing drugs in America.”

Over the past few years Allen Frances has become an outspoken critic of some psychiatric practices, including the overuse of antipsychotics and antidepressants. He’s also been critical of the DSM-5. He’s even written Saving Normal to address his concerns with psychiatry and psychiatric practice. Search for his name here to find several articles where he is mentioned.

I was surprised and encouraged to see Jeffrey Lieberman, the chair of psychiatry at the Columbia University College of Physicians and Surgeons express concern with the over prescribing of antipsychotics. Lieberman has positioned himself as defender of psychiatry and psychiatric practice, recently publishing Shrinks. You can also search his name here to see other articles interacting with his book and position on psychiatry. Lieberman said that antipsychotic medication should be used sparingly in treating nonpsychotic disorder, including depression. He said: “I think there’s the possibility that antipsychotics are overprescribed, not just for depression, but in other areas.”

My point is that when two prominent psychiatrists with opposing views on many areas of psychiatry and psychiatric practice agree that antipsychotics are overused, pay attention. Both Frances and Lieberman have pointed out elsewhere how pharmaceutical marketing strategies contribute to this problem, but some pharma companies and representatives put the blame back on doctors. An Eli Lilly spokesperson said pharmaceutical companies aren’t responsible for how their drugs are used by doctors. “Physicians make prescribing decisions, not pharmaceutical companies. . . . While certainly we inform doctors of the benefits and risks of our medicine, it’s really up to physicians to prescribe the right medicine.”

But this attempt to deflect responsibility onto physicians is a cop out when you consider the marketing done by pharmaceutical companies for their products. In this YouTube advertisement for Abilify as an antidepressant add-on, you see how Bristol-Myers Squibb actively encouraged individuals to “ask your doctor if Abilify is right for you.” Pay attention to the fact that the first thirty seconds verbally describes how Abilify can help, while the rest of the 90-second commercial has the woman and her family going on a picnic while the adverse side effects are described.

Another problem is that all clinical trials for drug approval are done over short periods of time—six or eight weeks—antipsychotics included. But what are the long-term consequences of antipsychotics? As Dan Iosifescu, the director of the Mood and Anxiety Disorders Program at Ichan School of Medicine at Mount Sinai Hospital said, “It’s just a fallacy to take short-term data and extrapolate it for long term.” His bottom line is that antipsychotics tend to be helpful in the short term, but can have major consequences in the long term.

Thomas Glasen, writing in Schizophrenic Bulletin, weighed the pros and cons of medication treatment for psychosis. In the case for medication, he noted that the benefits of medication were profound. The therapeutic power of antipsychotic medication had been validated in countless studies and was now the primary treatment of schizophrenia. “In today’s climate, treating schizophrenia without medication mobilizes high anxiety among treaters for the safety of their patients from irrationality and for the safety of themselves from litigation.” However, in the case against medication, Glasen said:

Antipsychotics obscure the pathophysiology of psychosis by altering the neurobiology of the brain and the natural history of [the] disorder. . . . Medication can be lifesaving in a crisis, but it may render the patient more psychosis-prone should it be stopped and more deficit-ridden should it be maintained.

So how do individuals on long-term antipsychotics do? In Anatomy of an Epidemic, Robert Whitaker described Martin Harrow’s presentation of a long-term study funded by NIMH on sixty-four individuals diagnosed as schizophrenic between 1975 and 1983. Whitaker had just reviewed a series of studies questioning whether there was a long-term benefit to the use of antidepressants before discussing the Harrow study. He then said: “If the conventional wisdom is to be believed, then those who stayed on antipsychotics should have had better outcomes.” Harrow found that after two years, there was evidence that the off-med group was doing slightly better than the group on drugs.

Then, over the next thirty months, the collective fates of the two groups began to dramatically diverge. The off-med group began to improve significantly, and by the end of 4.5 years, 39 percent were “in recovery” and more than 60 percent working.

The outcomes for the medication group worsened and this divergence continued. At the fifteen-year follow up, 40 percent of those off drugs were in recovery and more than half were working; only 28 percent suffered from psychotic symptoms. “In contrast, only 5 percent of those taking antipsychotics were in recovery, and 64 percent were actively psychotic.” The 2007 Harrow study can be found here. Harrow said that not only was there a significant difference in global functioning between the two groups, 19 of the 23 (83%) schizophrenic patients with uniformly poor outcome after fifteen years were on antipsychotics.

Harrow et al. (2014) continued his study and reported data in Psychological Medicine at the twenty-year stage of his follow-up schedule. Here he investigated whether multi-year treatment with antipsychotics reduced or eliminated psychosis; and whether the results were superior to individuals in the non-medicated group. The data showed that the pattern noted above by Whitaker in Harrow’s 2007 report continued: “A surprisingly high percentage of SZ prescribed antipsychotic medications experienced either mild or more severe psychotic activity.” The figure to the left, originally from the 2014 Harrow et al. report, shows that 68% of the medication group experienced psychotic activity, while only 8% of the off-med group experienced any psychotic activity. The source of the figure was a slide reproducing the Harrow data in a presentation by Robert Whitaker at the “More Harm than Good” conference sponsored by the Council for Evidence-Based Psychiatry (CEP). The slides and videos of the presentation can be found here.

Harrow et al. thought the high percentage of the medication group experiencing psychotic activity was influenced by two factors. One was the high vulnerability to psychosis of many schizophrenic patients, leading to a high risk of psychosis. But that begs the question of how the medication group in the study had such a high number of patients “at risk of psychosis.” Given the above data, their second factor seems to have been the more important factor: prolonged use of antipsychotics (or partial dopamine blockers) may produce a medication-generated build-up of supersensitive dopamine receptors or excess dopamine receptors.

The production of excess or supersensitive dopamine receptors would then be an iatrogenic, drug induced effect from the long-term use of antipsychotics. The brain increases or sensitizes the receptors, thus compensating for the blockade of original receptors in the postsynaptic neuron. Again, drawing from Whitaker’s presentation slides at the CEP conference, it would look like this:

The above presentation of Harrow’s data and the discussion from Whitaker’s CEP presentation seem to affirm Glasen’s thesis that antipsychotics could alter the neurobiology of the brain. Antipsychotics reduce the activity of dopamine systems, stimulating the increase of receptors. When the antipsychotic is tapered or withdrawn, this would not immediately diminish the number of additional dopamine receptors produced by the brain to compensate for the dopamine blocking action of the antidepressant. With decreased antipsychotic levels, the result would be increased activation of the postsynaptic neurons because of the greater number receptors to absorb dopamine.

The person’s symptoms could intensify through the increased absorption of dopamine because of this disregulation of the dopamine system. In other words, tapering off of antipsychotics could activate symptoms like mania, paranoia and hallucinations because of the chemical imbalance produced by the medication. The experience of mania from a too sudden withdrawal of an antipsychotic is in this view, likely a withdrawal or discontinuation symptom instead of proof that the person needs to remain on an antipsychotic because they have a chemical imbalance. Robert Whitaker’s conclusion in Anatomy of an Epidemic was:

What the scientific literature reveals is that once a person is on an antipsychotic, it can be very difficult and risky to withdraw from the medication, and that many people suffer severe relapses. But the literature also reveals that there are people who can successfully withdraw from the medications and that it is this group that fares best in the long term.

10/12/15

“Shake and Bake” Meth Labs

The DEA posted maps of the total number of meth lab incidents from 2004 through 2014. There were 23,829 total incidents in 2004; 6,858 in 2007; 13,432 in 2012; and 9,306 in 2014. Missouri, Tennessee and Iowa were the state with the highest amounts of reported meth lab accidents in 2004; Indiana, Missouri, and Tennessee for 2014. Many states throughout the US had dramatic decreases in reported accidents. That’s the good news. The bad news is that a CDC study indicates injuries from methamphetamine-related incidents are on the rise in some parts of the country.

The CDC report noted there was an increase of reported incidents from 2001 through 2004; followed by decreases through 2007; with increases again through 2012. In 7% of the meth-related incidents, 162 people were injured, including 26 children (16%). Among the injured, 136 (84%) were treated at a hospital, including 19 of the injured children. There were also two reported deaths: one probable meth cook and one law enforcement official.

The percentage of incidents with injured persons increased from less than 5% during 2001-2004 and 2005-2007 to 10% during 2008-2012. Most of the injuries were to members of the general public (97) and law enforcement officials (42). The most frequently reported injuries overall were: respiratory irritation, burns and eye irritation. Burn injuries were almost exclusively experienced by the general public, with 42 of the 44 reported injuries.

The researchers speculated that the initial declines in injuries were related to state and federal restrictions on the retail sales of common meth precursor drugs, ephedrine and pseudoephedrine. This was reversed in 2008 when meth cooks adapted by buying permitted quantities from multiple locations, often with false identification. Additionally, a new method for making meth became popular, one called “shake-and-bake.” This involves shaking smaller amounts of the precursor chemicals in a 2 liter plastic bottle. Unfortunately, the bottles frequently burst, causing burns and environmental contamination. “Burn injuries increased during this time, particularly to members of the public, who might have been meth cooks or household residents.”

Children who are present during the production of meth face many hazards. The Horton et al. study cited below reported that half the events with injured children occurred between midnight and 6 am, when most children are asleep. The authors speculated that sleeping children have an even higher risk of acute injury during an emergency event. “This is particularly true if the parents/care givers are in another part of the house and/or are under the influence of meth.” Several states have enacted laws to protect children from meth-related injuries.

A 2003 study by Horton et al. examined data from Hazardous Substances Emergency Events Surveillance (HSEES Events) identified eight children injured in meth events. “Five of the meth events with children occurred in private residences: three of which occurred in houses, one in an apartment building, and one in a duplex.” One of the children injured was 8 years-old. They concluded:

The HSEES data appear to indicate that the numbers of meth labs and associated emergency events will continue to increase, putting more children and other unsuspecting individuals at risk for hazardous substance(s) exposure. More action is needed to remove children from these dangerous environments and to educate innocent bystanders, as well as the substance abusers themselves, about the risks involved with meth and its illicit production.

A 2009 study by Thrasher et al., using case reports from the Washington State Poison Control Center found that a large proportion of meth lab exposures occurred in private households. Of the 198 exposed persons, 10.6% were meth cooks, 15.7% were law enforcement personnel, 35.4% were residents and 38.3% were classified as other. Twenty-eight of the reported exposures (19.2%) were children. “A subject’s own residence was the predominant site of exposure for cooks (71%), other adults (41%), and children (66%).”

Although the CDC study indicated recent increases in an increase in meth-related injuries, there is distinct likelihood the true incidence is significantly under reported. One limitation of the CDC study was that only five states were included. Now this was because those five states (Louisiana, Oregon, Utah, New York, and Wisconsin) were the only ones with complete information available for the time period 2001-2012. Another limitation was that meth incidents in homes were not included in the original data from the National Toxic Substance Incidents Program (NTSIP) unless there was a public health action, such as an evacuation.

	Total Meth Incidents 2004	Total Meth Incidents 2014
Oregon	632	1
Utah	107	1
Wisconsin	109	14
Louisiana	176	11
New York	136	197
Missouri	2,913	1,034
Tennessee	2,341	958
Iowa; Ohio (2014)	1,666	919
Illinois; Michigan (2014)	1,576	750
Indiana	1,377	1,471

One illustration of this under reporting can be seen by examining the incidents reported in the DEA maps for those five states included in the CDC study to the incidents in the five states with the highest reported incidents in 2004 and 2014. The five states included in the CDC study were: Oregon, Utah, Wisconsin, Louisiana, and New York. The five states with the highest reported incidents in 2004 were: Missouri, Tennessee, Iowa, Illinois, and Indiana. The five states with the highest reported incidents in 2014 were: Missouri, Tennessee, Indiana, Michigan, and Ohio. The total meth incidents for the five states in the CDC study, for 2004 AND 2014 were less than the incidents for just one of the top five states—for both 2004 and 2012. Another readily noticeable fact is that the highest incident states for both 2004 and 2014 cluster in the Midwest, with the border states of Tennessee and Kentucky thrown in for good measure.

We can say there was an increase for the five states included in the CDC study, but can’t assume that increase holds throughout the US. It is likely the real total is much higher, especially in the selected states from the DEA map noted here.

The Department of Justice has produced a handy pamphlet of “Fast Facts” about meth labs. It described signs to look for if you suspect the presence of a meth lab. These signs include: unusual odors; excessive trash, especially chemical containers, coffee filters, red stained pieces of cloth, and duct tape rolls. Other indications are secretive, unfriendly occupants; frequent visitors, esp. at unusual hours; curtained or blackened windows; extensive security measures or attempts to ensure privacy, such as “no trespassing” or “beware of dog” signs.

Meth labs come in all sizes. Super labs produce 10 pounds or more of meth at a time; smaller “box” labs produce as little as an ounce and can fit in a box or backpack. They can be located almost anywhere: private homes, hotels and motels, automobiles, boats and luggage. They can also be found in commercial and industrial districts; or nestled away in a secluded rural area.

The chemical used to produce methamphetamine are extremely dangerous. Some are very volatile and could ignite if not handled properly, as apparently was the case in the motel video mentioned below. Even if there is not fire or explosion, meth production is dangerous. Exposure to the chemical can pose a series of health risks, including respiratory problems, severe chemical burns, pulmonary edema, and more. Look at a table in the pamphlet listing various chemicals used in meth labs and the hazards associated with them.

Health Research Funding posting some facts about meth lab explosions and also had two embedded videos of meth lab explosions. One video shows a mobile home in a rural setting going up in smoke. The other captured an explosion in a motel room on a security camera. Seven burn units have shut down over the last six years because of the unreimbursed costs of treating burn victims in meth lab explosions. One pound of meth results in six pounds of toxic waste. Eighty percent of the meth labs found and dismantled by authorities used the “shake and bake” method.

The simplified “shake and bake” method and smaller size of these labs means that rolling meth labs in cars, trailers or mobile homes can be easily moved to a secluded location where the manufacturing fumes can’t be detected and the toxic waste discarded. In 2002, Interstate 24 in southwest Kentucky was temporarily shut down when a car containing anhydrous ammonia exploded. It was a rolling meth lab. “Trucking down the highway allows them to disperse the rotten egg smell the labs produce and keep the waste out of their own homes.” Of the 2,000 chemicals that could be used to make meth, at least half are explosive.

Illustrating how meth labs can be found anywhere, here is an article about an explosion that occurred at a federal facility in Gaithersburg, MD. The explosion happened on the main campus of the National Institute of Standards and Technology (NIST) on June 19th, 2015. Federal law enforcement officials found pseudoephedrine, drain opener and a recipe for making methamphetamine in the lab. Representative Lamar Smith wrote in a letter to the Commerce Secretary said: “I am troubled by the allegations that such dangerous and illicit activity went undetected at a federal research facility.”

10/9/15

Man’s God is Man

On August 3, 1948, Whittaker Chambers was called to testify before the House Un-American Activities Committee (HUAC). He gave the names of individuals he said were members of the Communist Party, including that of Alger Hiss. Chambers had himself been a Communist spy, but he became disillusioned during the Stalinist purges of the 1930s. He also reported a conversion to Christianity that led to his leaving the communist underground in 1938. By early 1948, Chambers had become one of the best known writer-editors for Time magazine.

Hiss was tried twice for perjury. He couldn’t be tried for espionage, because the evidence indicated the offense occurred more than ten years before that time and the statute of limitations for espionage was five years. The first trial ended with a deadlocked jury, eight to four for conviction. Chamber’s testimony was the primary evidence against Hiss. Hiss had an impressive array of character witnesses testify in his behalf, including two U.S. Supreme court justices, a former Democratic presidential nominee and a future Democratic presidential nominee, Adlai Stevenson.

Chambers was attacked by Hiss’s attorneys to discredit his testimony. They said he was: “an enemy of the Republic, a blasphemer of Christ, a disbeliever in God, with no respect for matrimony or motherhood.” At the second trail Hiss’s defense produced a psychiatrist who said Chambers was a psychopathic personality and a pathological liar. The second trial ended in January of 1950 with Hiss found guilty on both counts of perjury. He was sentenced to five years in prison, but only served three.

In 1952, Chambers published Witness, partly autobiographical, and partly a warning against the dangers of communism. It was a bestseller for more than a year and received wide acclaim. Ronald Reagan credited it as the inspiration behind his conversion from a New Deal Democrat to a conservative Republican. In 1984, then President Reagan posthumously awarded Chambers the Presidential Medal of Freedom.

Within Witness, Chambers said that Communism has a simple, rational faith that inspires men to live or die by it. This faith was humanity’s second oldest faith. Its promise was whispered during the first days of Creation under the Tree of the Knowledge of Good and Evil: “you will be like God.” This, he said, “is the great alternative faith of mankind.” Like all great faiths, its force is derived from a simple vision.

It is the vision of man’s mind displacing God as the creative intelligence of the world. It is the vision of man’s liberated mind, by the sole force of its rational intelligence, redirecting man’s destiny and reorganizing man’s life and the world.

Stripped of the rhetoric of the McCarthy era, Chambers does have a point. We can trace what he said here back to the thought of Ludwig Feuerbach, who wrote The Essence of Christianity in 1841. Feuerbach’s did have a significant influence on Karl Marx and his followers. Feuerbach argued against the existence of God, saying: “the mystery of theology is anthropology.” Man is the soul of God—“The Godhead of God is humanity.” Man has his highest being, his God, in himself. Not in himself as an individual, but in his essential nature.

If human nature is the highest nature to man, then practically also the highest and first law must be the love of man to man. Homo homini Deus est [man’s God is Man]—this is the great practical principle. This is the axis on which revolves the history of the world.

What Feuerbach wrote in 1841 and Chambers in 1952 is the heart of all sin and rebellion. In wanting to be wise, to know good and evil independent of the knowledge of God, humanity did make itself God. There is a wisdom that is “God’s sole preserve.” In his commentary on Genesis, Gordon Wenham said human beings should not aspire to attain it. “A full understanding of God, the universe, and man’s place in it is ultimately beyond human comprehension. To pursue it without reference to revelation is to assert human autonomy and to neglect the fear of the Lord, which is the beginning of knowledge (Proverbs 1:7).”

The tree of the knowledge of good and evil is only referred to by that name in Genesis 2:9 and 2:17. Genesis 2:9 contains the description of both the tree of life and the tree of good and evil being placed in the middle of the garden of Eden. In 2:17, the command that Adam should not eat from the fruit of the tree of the knowledge of good and evil “for in the day you eat of it you shall surely die” is given. In Genesis 3:6, it is referred to as a tree “to be desired to make one wise.”

Agreeing with Wenham, Kenneth Matthews said that the tree of the knowledge of good and evil was referring to a divine wisdom. He observed how several scholars have pointed out that features of the garden story in Genesis bear a strong resemblance to wisdom literature. The Wisdom tradition says that wisdom is possessed by God (Proverbs 2:6; 8:22); that it is something everyone should seek to attain (Proverbs 3:13; 8:10-11). Furthermore, it should be achieved through the “fear of the Lord” and by not by grasping for it independent of God (Psalm 111:10; Proverbs 2:1–6; 3:5–6; 9:10; 11:7, 29; 15:33; Isaiah 11:2).

By obtaining it through disobedience, the first couple expressed their independence of God and obtained wisdom possessed by God (3:5, 22) through moral autonomy. This autonomous action meant death because this wisdom was obtained unlawfully; transgression against the law of God carried the penalty of death.

When the garden setting is compared against the Mosaic tradition, there are several similarities. Commentators have pointed out where the two trees in the garden are comparable to the elements in the tabernacle that represent life and the law of God. The candlestick is shaped like a tree with its branches symbolizing life, while it gives light to the twelve loaves of bread representing God’s provision for Israel. The commands or “laws” of God is exemplified by the stone tablets in the ark of the covenant. “The God of the tabernacle was indeed the God of the garden.” Following the same line of thought as Matthews, Wenham said:

In the garden, the revealed law of God amounted to the warning “Do not eat this tree” on pain of death. In later Israel, many more laws were known, and those who flouted them incurred the divine curse and risked death. Since the law was God-given, it could not be altered or added to by man (Deut 4:2); thus human moral autonomy was ruled out (Josh 4:7). In preferring human wisdom to divine law, Adam and Eve found death, not life. In the tabernacle, the inviolability of the law was symbolized by storing the tables of the law inside the ark itself, the sacred throne of God, guarded and out of sight in the innermost holy of holies, for to see or to touch the ark brought death (Exodus 40:20; Numbers 4:15, 20.)

The heart of the Fall in the garden was to believe that homo homini Deus est, man’s God is Man. Chambers may not have been correct about Hiss, who continued to fight for and claim his innocence long after he was released from prison. But he was correct about the second oldest religion as one where man’s mind displaces God as the creative intelligence of the world. “It is the vision of man’s liberated mind, by the sole force of its rational intelligence, redirecting man’s destiny and reorganizing man’s life and the world.” Not communism, as Chambers said, but humanism, as Feuerbach said. Man’s God is Man.

Faith Seeking Understanding

Charles Sigler, D.Phil.

Monthly Archives: October 2015