Good news for people with combined depression and alcohol dependence

Depression combined with alcohol dependence has been a tough combination to treat, with a number of negative trials. However, a new trial of the combination of an antidepressant and naltrexone, a medication for treating alcohol dependence, showed excellent results. PI Helen Pattinati, PhD, is a well-respected and meticulous clinical scientist so one can be assured of proper attention to methodological detail. Also, since both drugs are generic, there is no drug company conflict of interest. (The downside to that is there is also no incentive to market the drug combination to doctors or consumers.)

PsychCentral.com

Treat Alcoholism and Depression Together

By Rick Nauert PhD Senior News Editor

Reviewed by John M. Grohol, Psy.D. on March 18, 2010
A new study discovers a treatment regimen combining cognitive-behavioral therapy and medications for depression and alcohol addiction improves clinical outcomes.

Specifically, combining the antidepressant sertraline (Zoloft) with the alcohol dependence treatment naltrexone produced a 54 percent abstinence rate in patients with both major depression and alcohol dependence, whereas the rates were only 21 to 28 percent for patients taking a placebo, sertraline only, or naltrexone only.

This study shows an important advancement in the treatment of patients who live with both alcoholism and depression because the co-occurrence of these disorders is common in clinical practice, yet antidepressants alone are not sufficient for reducing excessive drinking in these patients.

All 170 patients also received cognitive-behavioral therapy, and the four treatment groups all showed clinical reductions in depressive symptoms over the 14-week study, which was conducted by Helen Pettinati, Ph.D., and colleagues of the University of Pennsylvania.

In addition to a higher abstinence rate, the group receiving combination treatment had a longer interval before resumption of drinking: a median of 61 days compared with 15 days for the other groups combined.

Serious adverse events were actually less frequent in the group receiving both medications, since the most common serious event was hospitalization for detoxification or rehabilitation.

“When depression and alcohol dependence occur together, each condition has a negative influence on the outcome of the other, so not only does this pairing of illnesses affect a lot of patients, it also makes the individual disorders worse,” Dr. Pettinati stated.

“Combining sertraline and naltrexone could be a practical approach for these patients because both have FDA approval.”

The study appears in AJP in Advance , the online advance edition of The American Journal of Psychiatry (AJP), the official journal of the American Psychiatric Association.

Do computerized assessments and interventions work?

Here's a recent review of internet based assessment and intervention sites:

Journal of Substance Abuse Treatment

Volume 38, Issue 3, April 2010, Pages 203-211

Regular article

A review of computer-based alcohol problem services designed for the general public

Michael L. Vernon Ph.D., a,

a Alcohol Research Group, Emeryville, CA, USA

Abstract

This review summarizes the literature on computer-based drinking assessment and intervention programs evaluated using members of the general public. The primary aim was to summarize the demand, usage, and effectiveness of these services. A systematic search of the literature identified seven online drinking assessments and eight computerized interventions that were evaluated using members of the general public. Internet assessment users tend to be in their early 30s, are more often male, tend to be at risk for or are experiencing alcohol-related problems, more fully explore assessment sites, and are more likely to enroll in interventions linked to these sites when their drinking problem is more severe. Although dropout from computer-based interventions is often very high and treatment models vary widely, program completers appear to show improvements.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T90-4XY3KB6-4&_user=10843&_coverDate=04%2F30%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000000150&_version=1&_urlVersion=0&_userid=10843&md5=a4af488b2a9d2006da9fd4d063ed948c

Another new mechanism for medication treatment of alcohol dependence?

Here's an intriguing new study that suggests yet another novel mechanism of action for treating alcohol dependence:

 Alcoholics' Relapses Better Understood; Brain mechanism could be key, and an existing drug might help, scientists say

HealthDay

March 10, 2010

U.S. scientists say they've learned new details about molecular mechanisms associated with alcohol addiction and relapse. The findings could lead to new treatments for alcoholism.

The University of California, San Francisco researchers gave lab rats free access to alcohol or sugar for nearly two months, followed by a few weeks of abstinence. The rats who had consumed alcohol, but not those that had consumed sugar, showed increased electrical activity in a part of the brain called the nucleus accumbens (NAcb) core, which plays a role in motivation and goal-directed behaviors.

This increased activity in the NAcb core after abstinence resulted from the inhibition of small-conductance calcium-activated potassium channels (SK).

Futher tests showed that drug-induced activation of SK channels resulted in greater inhibition of NAcb activity in the alcohol-abstinent rats and significantly reduced their desire for alcohol. This type of effect did not occur with sugar-abstinent rats.

The results indicate that decreased SK currents and increased activity in the NAcb core play a critical role in alcoholics' relapse after quitting drinking, said the researchers.

The study appears in the March issue of the journal Neuron.

"Our findings are particularly exciting because the FDA-approved drug chlorzoxazone, which has been used for more than 30 years as a muscle relaxant, can activate SK channels," senior author Dr. Antonello Bonci said in a UCSF news release. "Although SK channels are not the only target of this drug and it can present a variety of clinical side effects, it provides an unexpected and very exciting opportunity to design human clinical trials to examine whether chlorzoxazone, or other SK activators, reduce excessive or pathological alcohol drinking."

What do medications add to recovery?

Do medications provide added value in addiction treatment? And, what is the downside, or potential cost, financially but more importantly on long term outcomes? I think this benefit/burden calculation is central to deciding whether they should be the standard of care or not. Opponents of medications question whether medications lead to “real” recovery, whether they are crutches, and why they are necessary when there is a clear path to recovery through AA. In many people there is an inherent gut response: “Why can’t you (or I) just stop? Isn’t taking a medication to treat a chemical addiction a contradiction in terms? Aren’t you just substituting one addiction for another?”

Let’s take a look at each question. Do medications lead to “real” recovery? It depends on how you define recovery. Most people would say that abstinence or even occasional use without problems would constitute recovery. Members of 12-step programs are more likely to assert that “real” recovery is abstinence plus something else that can only be obtained in 12-step programs: a spiritual transformation, or somewhat differently put, a major shift in values and character. My interpretation of what 12-step programs are aiming for is maturity. That is, the ability to love and be loved, to make a contribution to society, to be a good citizen of the world and to achieve a certain measure of acceptance of the world as it is and our place in it. From a medical standpoint the traditional goal of treatment is the absence of symptoms or signs of a disease, which is called remission (think of cancer.) I think 12-step “recovery” is remission plus maturity. Medical recovery is simply remission. This has implications for how one interprets the results of treatment studies, and also for how the boundaries of medical care are defined. I will write more about outcome measurement in another blog. However, for this discussion, I will adopt the assumption that the goal of professional treatment is remission, and that achieving personal growth and maturity is the responsibility of the patient.

So, if the goal of any treatment is remission, are medications effective? The unequivocal answer is yes. More people taking medications will achieve remission than those who do not. This is not a matter of personal opinion, but of scientific fact and clinical experience. Is every study positive? No. But more are positive than not, so it’s important to look at the totality (and quality) of all the studies. Look, a lot of people can stop smoking without any medication, but many other people require multiple attempts and multiple medications and counseling to quit. It’s no different for alcohol dependence. In the case of opioid (heroin, morphine, Dilaudid, Oxycontin) addiction, medication treatment is the only one showing consistent success. And in that case, long-term maintenance is usually required. So, the bottom line is: medications for treating addictions allow some people a chance at recovery who otherwise would fail at that quit attempt.

So, are these medications crutches, which implies that they are something for weak people and that one shouldn’t need them. Use of the term further implies that using them weakens the natural healing power, so that discontinuation will lead to relapse. Is there any evidence for that? Short answer: no. Unfortunately, most of the studies only provide a few weeks or months of medication treatment, so that they are discontinued at an arbitrary point rather than when it is best for the patient. Over time, after medication discontinuation, the positive medication effect fades so that the difference between medication and placebo groups decreases. However, there is no evidence that relapses suddenly rise after medication discontinuation. In fact, there remains an advantage in remission in the medication group as far out as one year even when treatment only lasted 16 weeks. In addition, at least as many people who are receiving medications also participate in community support groups like AA as those who are not. So there is no evidence that using them constitutes crutches in the negative sense of the term. Are they necessary? Well, for some people, the answer is yes. That is, they are unable to recovery without the aid of medications, at least for a specific quit attempt (most people have multiple quit attempts before one sticks.) Others don’t need them to stop. Are they substituting one addiction for another? The answer is yes, but only if you consider a diabetic addicted to insulin, or someone with high cholesterol addicted to lipid-lowering agents like statins. To me, the most important question is whether they are helpful to people and improve the odds of remission. If the answer to that is yes, and the burden or cost is reasonable, then they ought to be readily available to people. The medication treatment most often cited by medication opponents is long-term maintenance on methadone or buprenorphine (Suboxine, Subutex) for heroin or prescription narcotic addiction. Here the evidence is very stark: among those with established addiction (i.e., more than one year) long-term maintenance on an opioid medication is the only effective treatment. There are now dozens of studies, including high quality randomized controlled trials that have compared enhanced state-of-the-art behavioral treatment alone with medication-assisted treatment, and the answer is unequivocal. In my clinical work with this group of patients, I have concluded that after sufficient time addicted to opioids, the brain is changed in ways that are not reversible. In a way, this group of people suffers from an “opioid deficiency” which can only be treated with opioid supplementation.

Bottom line: Medications result in more people achieving remission (recovery) and in the case of established opioid dependence, they are the only effective treatment. They might be crutches, but when your leg is broken, you may need a crutch for a period of time to allow the bone to heal. Unfortunately, effective medications are only available for smoking cessation, alcohol dependence and opioid dependence. Unfortunately, there are no effective medications available yet for cocaine or methamphetamine or cannabis (marijuana) dependence. But there will be.

More information:

For alcohol dependence: www.niaaa.nih.gov/guide

For opioid dependence: http://csat.samhsa.gov/publications.aspx 

Smoking cessation: http://www.smoking-cessation.org/

More debunking of widely held assumptions

Here's another study that found that drinking did not affect the outcome of bipolar disorder. By the way, I disagree with the assumptions made by the authors that the directionality of the correlation between manic or hypomanic switching was from substance use to switching. To me, it makes more sense that people who are more likely to end up in a manic or hypomanic state are more likely to use alcohol and other substances to help cope with their mania.

MW

Am J Psychiatry.. [Epub ahead of print]

Impact of Substance Use Disorders on Recovery From Episodes of Depression in Bipolar Disorder Patients: Prospective Data From the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Ostacher MJ, Perlis RH, Nierenberg AA, Calabrese J, Stange JP, Salloum I, Weiss RD, Sachs GS; for STEP-BD Investigators.

Objective Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder. Method Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode. Results During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state. Conclusions Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study.