【SocialBeta 专访】复盘网易考拉海购刷屏 H5 背后，营销小爆款的打造机制是什么？
【SocialBeta 专访】复盘网易考拉海购刷屏 H5 背后，营销小爆款的打造机制是什么？
sherry　|　 15:50
第一支 Julia 戏精 H5 上线时，在网易考拉海购市场部负责人刘晓彬看来，这其实只是黑五大促期间传播计划之外的一个「小插曲」。「去年黑五大促，考拉市场部的工作之一，是完成一个『全球好物种草计划』，通过链接一批网红博主，在考拉的种草社区中沉淀一些优质内容进行带货。我们在工作过程中发现了一些可以自黑、有趣的吐槽点，于是想到了用一个 H5 来戏剧化地演绎这个任务的完成过程，顺势带出黑五大促的信息。」刘晓彬向 SocialBeta 介绍了 Julia 戏精系列 H5 最初的创意想法。如果你对第一支&H5&并不陌生，「找&500&个网红」正是初入职场的&Julia&接到的第一个任务，这个充满职场新人共鸣与代入感的槽点，在 H5 上线不久就占领市场人、营销广告人的朋友圈。营销圈有着最有好奇心又最爱吐槽的一群人。充满网感又爱吐槽的 Julia，以及「第一天入职就联系 500 多个 KOL」、「本来想吃食堂晚餐，但凌晨还没下班」的遭遇，让他们看到了自己的影子，也让这支从创意到制作仅花了 3 天就上线的 H5 ，在第一波营销人自来水的传播下，获得了不亚于大制作的刷屏效果。▲ 扫描二维码体验 H5其实在过去一年，我们不乏看到这样的案例。百雀羚的故事长图，招商银行的番茄炒蛋，腾讯公益的小朋友画廊，没有任何预告，在某个节点迅速占领大众的朋友圈。在一种刷屏的莫名之中，你打开了链接，「意想不到的有趣」或「不过如此，有什么值得转发的情绪」促使你成为了制造刷屏的环节之一。而相较于过去品牌动辄千万的品牌整合传播战役，它们可能只是一篇文章，一支短视频或 H5，但这并不妨碍它们成为年度刷屏案例。有一个词概括了这些刷屏案例——营销小爆款。不管是否准确，但「小」与「爆」确实概括了这类案例的两个特性：内容轻量但刷屏级传播。但在刘晓彬看来，决定一个作品能否成为小爆款，还是取决于是否建立在真实用户洞察基础上的精妙创意。小爆款能否「爆」，洞察成为关键故事讲给谁听，是否有共鸣？向左一步是转发，向右则是关闭，用户的选择只在一瞬之间，一支 H5 如何快速打动用户？Julia 初入职场的故事，就是让职场人找到自己的影子。年轻人有着个性多元的兴趣圈层，但职场人却是绝大多数年轻人的一个共同身份。职场不仅占据了生活中的主要场景，也成为情绪制造器：来自工作或上级的压力，同事相处间的槽点，让这个场域从不缺少话题与谈资。从刘晓彬的介绍中，从一开始，这支 H5 就并非是一个大众化的传播内容。Julia 的故事最初要打的目标受众就是市场人、营销人这样一群窄众群体。这群人既是 Social 圈最活跃的种子用户的圈层，本身也是网易考拉海购的目标用户。这个窄众群体往往会成为传播链条中的「扩音器」。意想不到的传播效果，让网易考拉海购开始有意识地在双十二大促时，围绕 Julia 继续打磨出一个吸睛故事，并有意识地加入了推广预算。▲ 扫描二维码体验 H51 月中旬，围绕 Julia 筹备年会的戏精故事的第三支&H5 《入职&55&天，我有了辞职的念头》上线（点击原文阅读体验），这可能也是 Julia 的告别演出。一个意外打造的品牌 IP，以第三支作为系列终结，刘晓彬介绍：「这也是考虑到用户的审美疲劳。同质化的故事或叙事手法必然导致用户兴趣点与关注度的下降。当然不排除有其他表现方式，比如用总监的番外篇或者其他人继续讲述考拉市场部的日常。」小爆款如何带货，品牌契合度更重要「Julia 的出现，最初更多是从品牌传播意义的角度去做的，原本只是期望做大促活动信息告知，但从我们预埋的电商卖货入口的导流和转化效果看，销售转化是大幅超过我们预期的。」刘晓彬告诉 SocialBeta。每一支故事中，网易考拉海购都给用户留了一个互动的入口，比如第一支的「帮猪你丫转正」，第二支的「帮猪你丫获得奖励」，而这些交互情节会直接导流至网易考拉海购的大促购买页面，以增强用户对故事的沉浸感，弱化品牌信息跳转的生硬。在第二支 H5 《入职半个月，网易爸爸让我怀疑人生》中，同样是大 Boss 与被「压榨」小职员的职场故事，误会了总监意图的 Julia 「被迫」做了一份&56&页的「双十二」好物清单。网易考拉海购尝试直接在故事中加入更多双十二大促的信息，也有意识地增加了猪厂等网易元素。这一重考量在于增强内容与品牌的相关性和契合度。「我们不希望内容做出来，后面贴任何一个品牌logo都可以。」这是刘晓彬及其团队在 Julia 系列 H5 中极力避免的。小爆款重点在于一个「小」字，内容轻量、有话题点或争议性，容易引发自传播，但品牌关联度与效果衡量也是其争议点所在。在 SocialBeta 看来，所有营销创意应该以终为始，紧扣品牌定位和价值主张，避免成为流于「自嗨」的形式主义，营销小爆款应该更多地成为以小博大的营销杠杆。4 重标准，探寻营销小爆款的打造机制网易市场部总经理袁佛玉曾在一次对外演讲中提到：在当下的用户环境中，最重要的是从机制上小爆款的产生成为常态。在打造出 Julia 系列的营销小爆款后，网易考拉海购如何制造出下一个营销小爆款。刘晓彬提到网易考拉海购在市场部成立的创意委员会，某种程度上可以理解为促进营销小爆款持续产出的一个「组织机制」：通过邀请网易内部资深市场人、品牌营销人，组成评审，从多个维度为团队的创意提案进行评估。你可以理解为这是一个团队内部的「提案比稿」与交流的形式，在刘晓彬的介绍中，创意委员会的出现某种意义上是为了解决营销碎片化的问题。「市场部同学的脑洞非常大，有许多天马行动的idea，如果不加以引导，我们日常的传播策划很容易陷入创意碎片化、品牌表达缺乏统一性的状态，这样就很难做出一些真正有价值、有影响力的案子。为了避免浪费资源做太多刚及格或 80 分的创意作品，所以我们就说用这种创意委员会的机制去做创意的筛选评估。」而评估的标准除了用户洞察、创意表现等维度外，内容与品牌调性是否契合，以及是否相关也格外重要。从网易考拉海购本身而言，作为网易系仅成立 3 年的年轻品牌，在借势网易本身的戏精、自黑风格迅速打开品牌知名度，并跨境电商行业占据名列前茅的市场份额后，其本身也正面临着品牌升级的转变，以及在品牌资产沉淀上的思考。换言之，借助这些刷屏案例，网易考拉海购想真正在消费者心中传递的品牌形象是怎样的？刘晓彬告诉 SocialBeta：「在树立『买进口，上考拉』功能导向的品牌形象后，考拉在接下来整体品牌塑造中，将会融入更多消费者的情感诉求，与目标用户的消费观和生活方式建立连接。」去年 11 月，网易考拉海购宣布与中信银行信用卡中心、中国移动、丰巣、花间堂、罗森、什么值得买等 9 家企业共同成立「美好生活联盟」，为消费者带来更多品质感的消费体验，借助跨界品牌营销的形式，网易考拉海购在不断提升品牌的价值。结语最后，当我们总结网易考拉海购刷屏 H5 背后营销小爆款的打造机制，有一点需要承认的是，随着营销的窄众与碎片化趋势愈演愈烈，用户的注意力与兴趣点越来越难以把握。一次洞察有效、创意工整、传播规范的 Campaign，其传播效果可能越来越不如一支有争议、有话题的 H5，从 ROI 或性价比而言，或许更是如此。因此，2017 年，在主流的营销传播现象之外，一股打造「营销小爆款」的风潮悄然袭来，而且似乎会在今年愈发明显。但 SocialBeta 认为，在褪去新奇创意、热点话题、刷屏传播的光环后，营销小爆款最终要走向服务品牌整体营销目标的母题，比起短暂的争议与热闹之后，品牌更应该考虑真正希望消费者记住什么。
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暂时木有评论美国精神病学协会2005年会(2005－5) 学术活动 | 39康复网 | 医源世界
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摘要: 美国精神病学协会2005年会
American Psychiatric Association
2005 Annual Meeting
美国乔治亚州亚特兰大
May 21 - 26, 2005, Atlanta......
专题推荐：
美国精神病学协会2005年会
American Psychiatric Association
2005 Annual Meeting
美国乔治亚州亚特兰大
May 21 - 26, 2005, Atlanta,
New Pharmacologic Approaches
to Addiction
Kathleen Brady, MD, PhD
This symposium focused on the
exciting and rapidly developing area of new pharmacologic
treatments for alcohol dependence.[1-8]
For many decades, alcoholism was primarily considered
a behavioral problem. As such, there was little
exploration of the neurobiology of alcoholism,
and the use of medications in treatment was uncommon.
In fact, until the early 1990s, disulfiram was
the only pharmacologic treatment approved by the
United States Food and Drug Administration (FDA)
for the treatment of alcohol dependence. Disulfiram
acts by inhibiting one of the primary enzymes
involved in the metabolism of alcohol, acetaldehyde
dehydrogenase, which leads to a build-up of the
metabolite acetaldehyde. This metabolite causes
uncomfortable physical symptoms. Disulfiram is
generally used to dissuade individuals from using
alcohol to avoid these uncomfortable symptoms,
rather than by decreasing the desire to use alcohol.
Over the last 10 years, however, there has been
an explosion in our knowledge about the neurobiology
of alcohol use, abuse, and dependence. This new
knowledge has led to a great deal of exploration
and rapid development of pharmacotherapeutic treatment
options for alcoholism. Naltrexone received FDA
approval for relapse prevention in alcohol dependence
in 1992, and acamprosate received approval in
early 2005. There are other agents under consideration
for approval by the FDA for the treatment of alcohol
dependence (ie, depot naltrexone), and controlled
trials of novel agents and combination therapies
are currently in progress.
The first talk in the symposium, presented
by Dr. Raymond Anton from the Medical University
of South Carolina, was entitled &The Neurochemical
Basis for Alcohol Pharmacotherapy.&[1-3]
Dr. Anton began with an elegant presentation
of recent data elucidating some of the neurobiological
systems involved in alcohol abuse and dependence.
Alcohol and all other known drugs of abuse produce
their reinforcing effects through activation
of dopamine reward pathways in the nucleus accumbens.
Higher cortical input also influences dopaminergic
activity in the nucleus accumbens with important
connections from the prefrontal cortex, cingulated,
and amygdala. Glutamatergic input to the nucleus
accumbens is also critical in modulating dopamine
release. It appears that different neural pathways
are involved at different stages of alcohol
dependence. As alcoholism progresses over time,
changes in brain pathways lead to increased
sensitivity to the salience of drug-related
cues and stress in vulnerability to relapse.
These changes in brain pathways have been called
&sensitization& because they involve
the development of greater responses to same
stimuli over time. The gamma-amino-butyric acid
systems (GABA) and glutamate systems are involved
in the early stages of addiction and in the
development of alcohol withdrawal. The dopaminergic,
cannabinoid, and opioid systems appear to be
involved in reward memory and craving. Naltrexone,
an opiate antagonist that has demonstrated efficacy
in relapse prevention in alcohol-dependent individuals,
decreases dopamine release stimulated either
by alcohol or alcohol-related cues.
There is a great deal of individual vulnerability
in the effects of alcohol and the development
of alcohol withdrawal. The genetic vulnerability
to alcohol dependence may also play a role in
medication response. In one study comparing
alcohol-dependent individuals with or without
a family history of alcohol dependence, individuals
with a positive family history had a greater
increase in B-endorphin levels in response to
alcohol consumption and a better response to
naltrexone treatment. Of interest, a depot form
of naltrexone has also demonstrated efficacy
in preventing relapse in alcohol-dependent individuals.
One injection of this agent is active for approximately
3 to 4 weeks. Depot naltrexone is currently
under FDA review for the treatment of alcohol
dependence. Acamprosate, a drug that has recently
received FDA approval for alcohol relapse prevention,
acts through modulation of glutamatergic function.
In a series of clinical trials conducted in
Europe, acamprosate treatment was associated
with increased abstinence rates and increased
time to first drink in alcohol-dependent populations
when compared with placebo. In a multisite trial
in the United States, acamprosate demonstrated
efficacy in alcohol-dependent individuals who
had at least 5 to 7 days of abstinence prior
to medication initiation and a strong commitment
to abstinence at the initiation phase of the
trial. Topiramate, another medication that acts
primarily through the glutamatergic system,
has also been shown to decrease alcohol consumption
and increase the number of individuals who attained
abstinence compared with placebo in a group
of alcohol-dependent individuals.
The second talk, given by Dr. Henry Kranzler
of the University of Connecticut Health Center,
was entitled &Matching Serotonergic Medications
to Alcoholism Subtypes.&[4]
Animal studies are fairly consistent in demonstrating
that serotonergic (5-HT) agonists, such as the
selective serotonin reuptake inhibitors (SSRIs),
decrease alcohol consumption. However, data
from human laboratory studies and clinical trials
are much less consistent, and careful examination
of data from any single study generally shows
a great deal of variability of response, with
some individuals showing decreased alcohol consumption
and others showing increased consumption. In
one placebo-controlled study of fluoxetine for
relapse prevention in alcohol dependence,[5]
no difference was found in alcohol-related outcomes
between treatment groups.
A post-hoc analysis looking at medication effects
based on subgroups found that for Type B alcoholics,
characterized primarily by earlier onset of
drinking, drinking measures were increased in
the fluoxetine group during the 12-week treatment
period compared with placebo. Several subsequent
studies have concurred with this finding in
demonstrating that early-onset alcoholics do
not show decreases in drinking with SSRI treatment,
and sometimes drink more during treatment with
SSRIs compared with placebo. However, several
studies have demonstrated that alcohol-dependent
individuals with a later onset of illness (age
& 25 years.) show decreased drinking with
SSRI treatment compared with placebo. In another
recent study highlighting the complexity of
the relationship between subtypes of alcohol-dependent
individuals and 5-HT systems, ondansetron, a
5HT-3 antagonist, was found to decrease alcohol
consumption in individuals with early-onset
alcohol dependence.
Psychiatric comorbidity, especially depression,
is common in alcohol-dependent individuals.
Another method of subtyping alcohol-dependent
individuals for the purpose of individualizing
treatment is to consider psychiatric comorbidity.
In a recent meta-analysis by Nunes and colleagues,[6]
14 placebo-controlled trials of antidepressants
in subjects with comorbid substance dependence
and major depression were reviewed. Eight of
these studies were conducted in alcohol-dependent
individuals. They found a small to moderate
effect size for antidepressants in decreasing
alcohol consumption in depressed alcoholics.
However, in those studies that demonstrated
a decrease in depression, a decrease in alcohol
consumption also occurred. These decreases suggest
that the use of medications for the treatment
of depression in depressed alcoholics should
always be considered.
Dr. Kranzler and his research group have been
using an experimental paradigm which involves
the rapid depletion of tryptophan, the primary
dietary precursor of 5-HT, to study the role
of 5-HT in alcoholism.[4] Tryptophan
depletion paradigms have been used in the study
of depression where it has been demonstrated
that exacerbation of depressed mood after rapid
tryptophan depletion is a predictor of positive
response to SSRI treatment. Kranzler and colleagues
found that tryptophan depletion in depressed
alcoholics was associated with an increase in
alcohol craving. They also found that, similar
to the data from depressed individuals without
alcohol dependence, depressed alcohol-dependent
individuals who respond to rapid tryptophan
depletion with an exacerbation of depressed
mood have a more robust response to SSRIs. As
such, the rapid tryptophan depletion paradigm
offers hope for making evidence-based decisions
concerning the use of SSRIs in alcohol-dependent
individuals. Because of the variability in response
to SSRIs in alcohol-dependent individuals and
the possibility that for some individuals SSRIs
may actually increase alcohol consumption, predictors
of SSRI response are particularly important.
Dr. Bankole Johnson, from the University of
Texas Health Science Center, gave a talk entitled
&Combination Medication Strategies for
Alcoholism.&[7] Dr. Johnson
stressed the complexity of the neurobiology
of alcoholism and the involvement of different
neurotransmitter systems in the development
and maintenance of alcohol abuse and dependence.
The medications developed thus far to treat
alcohol dependence act on different neurotransmitter
systems, providing a strong rationale for the
use of combination therapy. While placebo-controlled
trials have demonstrated efficacy for both naltrexone
and acamprosate, the effect size for both agents
is small. With combination therapy, there may
be an increased effect size and synergy between
agents because of the action at different sites
involved in the pathophysiology of alcohol dependence.
However, combination therapy can also lead to
an increase in adverse effects and the possibility
that the effects of one agent may antagonize
the effects of the other. Acamprosate primarily
acts through the glutamatergic system, and naltrexone
is an opiate antagonist. In one study of combined
naltrexone and acamprosate, naltrexone alone
had a greater effect than acamprosate alone,
and the combination only showed modest benefit
compared with naltrexone alone. In another medication
combination study, the combination of ondansetron
and naltrexone was found to be superior to placebo
in decreasing alcohol consumption. Unfortunately,
there was no direct comparison of the two agents
alone to the combination treatment in this study,
making the results difficult to interpret.
Topiramate, another glutamatergic antagonist
that has demonstrated efficacy in decreasing
alcohol consumption in alcohol-dependent individuals,
was studied in combination with ondansetron.
The combination had a larger effect than either
agent alone. When ondansetron was added to topiramate,
there was only a small enhancement of treatment
effect. However, when topiramate was added to
ondansetron, there was a large increase in effect
size. The reason for this difference is not
clear. Dr. Johnson stressed the importance of
human laboratory studies in exploring interactions
and possible toxicities of medication combinations.
The final speaker was Dr. Aiti-Daoudi, from
the University of Texas Health Science Center,
who spoke about the &Relationship Between
Serotonin Transporter Function and Craving.&[8]
Dr. Aiti-Daoudi described a human laboratory
study in which alcohol-dependent individuals
were exposed to alcohol-related cues, and the
craving for alcohol was measured. The rapid
tryptophan depletion paradigm, described above,
was utilized. In addition, a functional polymorphism
of the serotonin transporter gene (SERT) was
also examined in all study participants. It
has been previously reported that individuals
with the short allele (SS) of SERT are more
susceptible to the development of depression
after experiencing environmental stressors compared
with those with long allele (LL). Dr. Aiti-Daoudi
and colleagues found that SS individuals had
increased craving when exposed to alcohol-related
cues after tryptophan depletion, and LL individuals
had decreased craving. This study provides preliminary
evidence for another promising paradigm to help
in subtyping alcohol-dependent individuals for
the purposes of individually tailoring treatment
to optimize treatment response.
Dr. Michael Gendel, from the University of
Colorado, was the discussant for this symposium.
He praised the extraordinary advances that have
been made in understanding the neurobiology
of alcohol dependence and in expanding treatment
options. Unfortunately, much of this growth
in our knowledge base has occurred during a
time of shrinking resources. Both private and
public sector funding for treatment of mental
health and addictions has been decreasing. Recent
studies of the addiction treatment system in
the United States have concluded that there
is insufficient training, organization, and
reimbursement for treatment and, as a result,
the organization, administration, and personnel
infrastructure of many programs are fragile.
Unfortunately, without increased support for
treatment, new developments will not be implemented
and even the best medications can only be useful
if they are accessible to the individuals who
need them. In the current healthcare environment,
treatment of substance use disorders is often
beyond the reach of many of the individuals
who most need treatment. In efforts to improve
the treatment of substance use disorders, attention
to healthcare policy and financing will be important
in assuring that the extraordinary advances
in the understanding of the neurobiology of
addictions can be translated into improvements
in the quality of healthcare.
In conclusion, great discoveries have been
made in the past 10 years that have contributed
to our understanding of the neurobiology of
alcohol dependence. This has improved and expanded
treatment options but has also elucidated the
complexity of the disorder and revealed the
multiple pathways involved. Descriptive and
clinical case studies have noted the various
presentations and heterogeneity of alcohol use
disorders.
Pharmacotherapeutic treatment trials have also
highlighted this heterogeneity as a result of
variability in treatment response. Human laboratory
paradigms and genetic testing show promise in
providing data to assist in rational subtyping
to choose the best treatment to optimize treatment
outcomes. There is good rationale for combining
medications to optimize treatment outcomes,
and preliminary studies are promising. Yet,
cautious optimism should be mixed with a healthy
dose of skepticism. We must continue to advocate
for the survival of the treatment system and
for increased support of treatment for mental
health and substance use disorders so that these
scientific advances can be put into practice.
References
Anton RF. Neurochemical basis for alcohol
pharmacotherapy. Program and abstracts of
the American Psychiatric Association 2005
Annual M May 21-26, 2005; Atlanta,
Georgia. Symposium No. 10A.
Anton RF, Swift RF. ) Current pharmacotherapies
of alcoholism: a U.S. perspective. Am J Addictions.
Anton RF, Moak DH, Waid LR, Latham PK, Malcolm
RJ, Dias JK. Naltrexone and cognitive behavioral
therapy for the treatment of outpatient alcoholics:
results of a placebo-controlled trial. Am
J Psychiatry. 8-1764.
Kranzler HR. Matching serotonergic medications
to alcohol subtypes. Program and abstracts
of the American Psychiatric Association 2005
Annual M May 21-26, 2005; Atlanta,
Georgia. Symposium No. 10B.
Kranzler HR, Burleson JA, Korner P, et al.
Placebo-controlled trial of fluoxetine as
an adjunct to relapse prevention in alcoholics.
Am J Psychiatry. -397.
Nunes EV, Levin FR. Treatment of depression
in patients with alcohol or other drug dependence.
A meta-analysis. JAMA. 7-1896.
Johnson BA. Combination medication strategies
for alcoholism. Program and abstracts of the
American Psychiatric Association 2005 Annual
M May 21-26, 2005; Atlanta, Georgia.
Symposium No. 10C.
Ait-Adaoud N. Relationship between 5HT transporter
function and craving among Hispanic patients
with alcoholism. Program and abstracts of
the American Psychiatric Association 2005
Annual M May 21-26, 2005; Atlanta,
Georgia. Symposium No. 10D.
in Dual Diagnosis
Ihsan M Salloum, MD, MPH &&
Introduction
Frequency and Impact of &Dual Diagnosis&
Psychiatric disorder and substance abuse comorbidity
is highly prevalent in the community and also
in the clinical population. Several large epidemiologic
surveys over the past 2 decades have consistently
reported that individuals with psychiatric disorders
have higher rates of substance use disorders,
and those who have substance use disorders have
higher rates of psychiatric disorders.[1-3]
For example, the Epidemiological Catchment Area
Survey has found a lifetime rate of 13.5 % for
alcohol use disorders among the general population.
The rate of alcohol use disorders increased
to 16.5 for major depression, 21% for dysthymic
disorder, 24% for obsessive-compulsive disorder,
29% for panic disorder, 34% for individuals
with schizophrenia, and the highest rates among
the major psychiatric disorders were found for
bipolar II (39%) and bipolar I (46%) disorders.[1]
The more recent surveys of nationally representative
samples, the National Comorbidity Survey[2]
and the National Institute on Alcohol Abuse
and Alcoholism's National Epidemiologic Survey
on Alcohol and Related Conditions (NESARD),[3]
the largest survey to date, have reported similar
findings for lifetime[2] and 12-month[3]
Comorbid psychiatric and substance abuse disorders
present with significant clinical challenges
and have a negative impact on treatment adherence,
treatment response, course, they
lead to increased service utilization, morbidity,
and mortality. Efforts at improving treatment
interventions are ongoing, however, and the
treatment needs for this population remain largely
unmet. Furthermore, tobacco smoking and nicotine
dependence, a major comorbid substance use disorder
among individuals with psychiatric disorder,
have received much less attention by the mental
health and the substance use treatment communities.
Some of these issues were discussed at the American
Psychiatric 2005 Annual Meeting in Atlanta,
Pharmacologic Treatment of Comorbid Substance
Use Disorders and Psychiatric Disorders
Treatment of comorbid psychiatric and substance
use disorders pose multiple challenges. These
comorbidities represent a wide array of conditions
that are likely to begin in adolescence and
co-occur over the life span. &Dual diagnosis&
patients are more likely to be over-represented
in treatment settings, as individuals suffering
from more than 1e disorder are more likely to
seek care. Clinicians caring for this population
are faced with a key concern
is the selection of effective treatment. Evidence-based
treatment for most psychiatric and substance
use comorbidities is a developing field, and
we still have limited options to guide treatment
selections. Francis Levin, MD[4]
Associate Professor of Psychiatry Columbia University/College
of Physicians and Surgeons/New York State Psychiatric
Institute, reviewed these issues at the APA
Dr. Levin's review focused on pharmacologic
treatment approaches of common comorbid psychiatric
disorders among individuals with substance use
disorders. These included comorbid depressive
disorder, bipolar disorder, anxiety disorders,
and attention deficit/hyperactivity disorder
Optimizing treatment of psychiatric disorders
is essential to improving the outcome of the
substance use disorder. It has been long documented
that high psychiatric severity predicts poor
substance use treatment outcome.[5]
Several studies have shown that psychiatric
disorders may worsen treatment outcome of substance
use disorders. For example, depressed patients
tend to do worse in treatment.[6,7]
Also, patients with depressive disorders are
more likely to relapse to alcohol use earlier
than those without major depression.[8]
Rapid relapse subsequent to substance use treatment
has also been documented among adolescents with
major depression.[9] Patients suffering
from posttraumatic stress disorder (PTSD) have
poor treatment response.[10] Similarly,
substance abusers with ADHD do worse in treatment,
are less successful in attaining treatment goals,
and are less likely to graduate from therapeutic
communities.[11]
Furthermore, the presence of a comorbid condition
increases the overall symptom burden. Individuals
with mania and alcoholism were found to have
significantly higher incidence of symptoms of
impulsivity, mood lability, violent behavior,
and other drugs of abuse compared with those
with mania but without alcoholism.[12]
Female patients with bipolar alcoholism reported
heightened burden of depressive symptoms as
well.[13] The presence of substance
abuse disorder also increases the risk of suicidal
behavior among patients with severe psychiatric
disorders, such as those with major depression,
bipolar disorder, and schizoaffective disorders.[14]
Moreover, a longitudinal study found that individuals
with prior history of alcohol dependence had
a 4-fold increase in the incidence of current
major depressive disorder.[15]
Treatment of these patients requires combined
attention to both psychiatric and substance
use disorders. Addressing only 1 disorder usually
leads to treatment failures, poor response,
and treatment dropout, resulting in worsened
prognosis.[4] Treatment also generally
requires a combination of counseling and pharmacotherapy.
Several nonpharmacologic interventions may be
used in these patients. These include the Minnesota
model, motivational enhancement therapy, relapse
prevention, contingency management, and integrative
case management.[4] Despite the high
frequencies of these comorbid conditions, well-controlled
pharmacologic trials are still scarce. Comorbidity
of major depression with substance use disorders
is the most studied to date. Fewer studies are
available for comorbidity with anxiety disorders,
and fewer still have been conducted in comorbid
bipolar disorder or comorbid ADHD.
Treatment of Major Depression in Comorbid
Substance Use Disorders
This form of comorbidity is highly prevalent
as both major depressive disorder and substance
use disorders are among the most frequent psychiatric
disorders in the community.[1] As
described by Dr. Levin, more studies have been
conducted evaluating different pharmacologic
agents for this form of comorbidity. Dr. Levin
presented the results of a recent meta-analysis
on treatment of comorbid depression and substance
use disorder.[16] Fourteen well-controlled,
randomized, double-blind, placebo-controlled
studies were analyzed.[16] The majority
of these studies addresse
other studies focused on cocaine dependence
alone or cocaine dependence among methadone
maintenance patients. Four studies evaluated
the efficacy of the antidepressant imipramine,
4 studies evaluated the efficacy of sertraline,
3 studies evaluated the efficacy of fluoxetine,
and 3 studies focused on 1 medication each (desipramine,
nefazodone, and viloxazine). Methodologic differences
between these studies were noted. For example,
some studies had periods of enforced abstinence
prior to making the diagnosis of major depression,
while others did not. Also, there were large
variations in placebo-response rate among these
studies. Studies with higher placebo rate were
less likely to find a medication effect. On
the other hand, most of these studies used common,
standardized measures for depression and alcohol/drug
use outcomes. The pooled data from all of these
studies included fewer than 850 subjects. The
results of this meta-analysis showed that there
was a modest overall beneficial effect for the
depressive symptoms among these patients. Improvement
in substance use correlated with improved depression
regardless of medication response. In those
studies that had a large effect size in improving
depression, there was also an effect on substance
use. It was also noted that there were high
placebo-response rates in those studies that
included nonabstinent populations or when a
history of long-standing depression was not
ensured. These latter findings may indicate
higher rates of drug-induced depression in those
samples and emphasize the importance of ascertaining
the primary nature of the major depressive disorder
prior to initiating pharmacotherapy.
Thus, although a number of clinical trials
have been completed in comorbid depression and
substance use disorders, pharmacologic approaches
that are clearly effective for both the depression
and the substance use disorders are still lacking.
Treatment of depression in substance-abusing
patients may be best accomplished by utilizing
agents that are best tolerated, with a safe
adverse event profile, and that are less likely
to interact with abused substances.
Treatment of Bipolar Disorder in Comorbid
Substance Use Disorders
Dr. Levin explained that there is little empirical
evidence to guide treatment for comorbid bipolar
disorders and substance abuse. This population
presents the additional challenge of a particularly
serious lack of treatment adherence. A number
of open-label pilot studies with different compounds
have reported conflicting results. Results from
open-label studies are subject to multiplicity
of confounds. Only 3 controlled trials have
been published to date. A double-blind pilot
study of 25 adolescents reported an advantage
of lithium carbonate over placebo on the urine-positive
screen (mostly marijuana) and also on mood symptoms.[17]
Adolescent-onset bipolar disorder may be a significant
risk factor for the development of substance
use disorder[18]; thus, effective
treatment of adolescent-onset bipolar disorder
should be particularly beneficial in the prevention
of substance use among these patients. To date,
there has been no replication of this study.
The efficacy of carbamazepine in cocaine dependence
was evaluated in a sample of 139 adult subjects
over a 12-week period. Of the total sample,
57 subjects had a history of
almost half of them had bipolar spectrum disorder.
In these subjects, carbamazepine was better
than placebo in reducing cocaine use as measured
by self-report and urine drug screen, and there
was a nonsignificant trend toward time to relapse
to first cocaine use.[19]
Only 1 randomized clinical trial has been published
to date with a group of adult subjects presenting
in an acute bipolar episode (depressed, mixed,
or manic) and active alcohol dependence. This
24-week double-blind, placebo-controlled trial
evaluated the efficacy of valproate compared
with placebo in patients who were stabilized
on lithium carbonate and received weekly individual
dual diagnosis counseling. Valproate was significantly
better than placebo at reducing the percentage
of heavy drinking days and time to relapse to
sustained heavy drinking. Higher valproate blood
levels correlated with improved alcohol outcome.
Manic and depressive symptoms improved equally
in both groups.[20] It is clear that
more evidence-based treatment approaches need
to be evaluated for this form of comorbidity.
Other potentially useful agents, such as newer
anticonvulsants or novel antipsychotics, have
not been tested yet in this population.
Treatment of Anxiety Disorders in Comorbid
Substance Use Disorders
Anxiety disorders include disorders that may
present different challenges when co-occurring
with substance use disorder. For example, diagnostic
difficulties may be quite high when considering
the diagnosis of generalized anxiety disorder
in the context of substance use, as most substance
intoxication or withdrawal states may mimic
the symptoms of generalized anxiety disorders.
Generalized Anxiety Disorders
However, in terms of pharmacologic treatment,
generalized anxiety disorder and comorbid alcoholism
has received the most attention. Dr. Levin explained
that 3 double-blind, placebo-controlled studies
evaluating buspirone have been published to
date.[21-23] Buspirone was found
to decrease anxiety symptoms in 2 of these studies,[21,23]
especially in those subjects who reported severe
anxiety at baseline.[23] One study
reported decreased desire to drink and improved
functioning as well.[21] Another
study reported a significant advantage of buspirone
over placebo with regard to subjects' retention,
time to first heavy drinking day during the
acute treatment phase, and reports of number
of drinking days at 6-month follow-up.[23]
No differences between buspirone and placebo
with regard to either anxiety or alcohol outcome
were found by the third trial.[22]
Thus, there are conflicting reports on the
efficacy of buspirone in alcoholism with co-occurring
generalized anxiety disorder. Subgroups of patients
with alcoholism and comorbid severe initial
anxiety symptoms may benefit
however, there have been no follow-up trials
assessing the efficacy of buspirone in subgroups
of alcohol-dependent patients. The advantage
of buspirone, explained Dr. Levin, is that buspirone
has no abuse potential. It also has a low side-effect
profile and is easy to discontinue. However,
it has slow onset and often requires an increase
to the higher therapeutic dose. Also, there
seems to be low level of acceptance by patients.
Social Anxiety Disorder
Only 1 published randomized, double-blind,
placebo-controlled pilot study has evaluated
the efficacy of paroxetine in patients with
comorbid social anxiety and alcohol use disorders.
Fifteen subjects were randomized to paroxetine
(flexible dose, up to 60 mg/day) vs placebo
and followed for 8 weeks. There was a significant
advantage of paroxetine over placebo with regard
to improvement in social anxiety symptoms and
improvement rated on the clinical global impression
scale for alcohol use. However, the 2 groups
did not differ with regard to the quantity/frequency
of reported alcohol use.[24]
Posttraumatic Stress Disorder
Only 1 randomized clinical trial has been published
to date describing comorbid PTSD and alcohol
dependence.[25] This double-blind,
placebo-controlled trial of 94 individuals evaluated
sertraline (150/mg day) vs placebo over a 12
week-period. A differential response to sertraline
vs placebo was found. Subjects with less severe
alcohol dependence and early-onset PTSD who
were randomized to sertraline reported significantly
fewer drinks per drinking day than those randomized
to placebo. By contrast, subjects with more
severe alcohol dependence and late-onset PTSD
and who were randomized to sertraline reported
significantly worse outcome with regard to the
number of drinks per drinking day than those
randomized to placebo.
The results of this study highlight the heterogeneity
of treatment response among different subgroups
of alcohol-dependent subjects and the intricacy
of psychiatric and alcoholism interaction in
terms of mediation of treatment response. Responders
to sertraline in this group had a longstanding
history of PTSD while their alcoholism was less
severe. This may support the observation that
optimizing treatment of the primary psychopathology
would lead to improvement in alcohol outcome.
Treatment of Attention Deficit/Hyperactivity
Disorder in Comorbid Substance Use Disorders
Dr. Levin explained that individuals with ADHD
have an earlier age of onset of substance use
disorders, and substance dependence is less
likely to remit than in those without ADHD.
Also, a number of clinical epidemiologic studies
have reported high prevalence of ADHD in clinical
samples of treatment-seeking substance abuse
populations, with rates ranging from 15% to
24%.[4] A number of case reports
and open trials using a variety of medications
have been published, but only a few randomized,
controlled trials have been reported to date.
One randomized, double blind, placebo-controlled
study evaluated the efficacy of pemoline (75
to 112.5 mg/day) in 69 adolescents (aged 13-19)
with ADHD, substance use disorders, and conduct
disorder (CD), over a 12-week period. There
was an advantage of pemoline over placebo in
decreasing ADHD symptoms. However, pemoline
was not better than placebo with regard to substance
use or CD outcome.[26] Another 12-week,
double-blind, placebo-controlled trial of methylphenidate
(MPH) in 48 individuals with comorbid ADHD and
cocaine dependence reported an advantage of
MPH over placebo with regard to proportion of
subjects with clinical global impression rating
of 1 or 2. However, there were no differences
between the 2 groups with regard to other outcomes,
including several measures of cocaine use. There
was also no worsening in cocaine use for subjects
participating in the study.[27] The
efficacy of sustained-release MPH was evaluated
in a recent 14-week, double-blind, placebo-controlled
trial in 90 adult subjects with comorbid cocaine
dependence and ADHD.[4] There was
no difference between the 2 groups with regard
to ADHD symptoms. On the other hand, there was
a reduction in cocaine use for patients treated
with MPH.[4]
Dr. Levin discussed that there was not a simple
answer for the question of whether stimulants
should be used in patients with substance use
disorders. Other medications with no abuse potential
may be tried first. Atomoxetine is the only
nonstimulant medication approved by the United
States Food and Drug Administration (FDA) for
the treatment of ADHD and is a reasonable first
choice. Those with current or past substance
abuse should be involved in ongoing substance
use treatment programs and should attempt to
establish a period of abstinence. Also, a careful
history of amphetamine or other stimulant abuse
should be determined. Furthermore the patient's
reliability should be carefully assessed. Also,
the presence, availability, and willingness
of a family member or close associate without
a substance abuse problem should be sought for
involvement in the treatment plan. The treatment
team should ensure that the patient and family
members are adequately informed about the potential
risks of stimulant therapy. Long-acting preparations
should be used, with emphasis on medications
taken on a regular basis rather than on an as-needed
Treatment of Cannabis Abuse and Psychosis
Cannabis abuse is a significant problem among
individuals with psychotic disorders. The comorbidity
and treatment of cannabis use disorder with
psychosis was discussed by Alan I. Green, MD,[28]
Professor and Chairman, Department of Psychiatry,
Dartmouth Medical School.
Epidemiologic surveys have documented that
47% of patients with schizophrenia have substance
use disorders. Alcohol, cannabis, cocaine, and
nicotine are the primary substances of abuse
in schizophrenia. The rate of cannabis use disorders
among first-episode patients is substantial,
with some studies reporting rates up to 50%.[29]
Longitudinal studies have indicated that up
to 63% of first-episode schizophrenia patients
have used cannabis prior to psychosis and 53%
have concurrent cannabis use with the development
of psychosis.
Several hypotheses are advanced to explain
the high association between substance use disorders
and schizophrenia. This may include a potential
causal link between cannabis use and the development
of schizophrenia, and whether cannabis increases
the vulnerability to schizophrenia. Studies
have shown an earlier age of onset of schizophrenia
in cannabis users.[30] Also individuals
with schizophrenia may be prone to use cannabis
as a form of self-medication. Patients with
schizophrenia may have mesocorticolimbic dopamine
system dysfunction leading to reward deficit
that could predispose them to cannabis and other
substance abuse.
The association of cannabis with schizophrenia
leads to many negative consequences, including
earlier onset of schizophrenia, increased relapse,
treatment noncompliance, poorer overall response
to antipsychotic medication, more hospitalizations,
increased risk for violence, and increased medical
costs.[28] Despite these negative
consequences, treatment of cannabis abuse has
been generally underemphasized in the psychiatric
treatment setting, and cannabis abuse is not
addressed unless it clearly interferes with
treatment. It is important to address cannabis
use in this population, as cannabis abuse is
associated with earlier age of onset and delays
treatment of psychosis. Certain psychosocial
treatments such as contingency management appear
to be helpful in decreasing cannabis use among
these patients. Treatment programs that integrate
attention to both disorders, including pharmacotherapy
and substance abuse psychosocial services, may
best address the need for these patients.
Studies of pharmacotherapy for comorbid cannabis
use in patients with schizophrenia have shown
that typical antipsychotics are of limited value
in controlling the substance abuse. Comorbid
patients have shown poor response to these medications,
with increased incidence of extrapyramidal side
effects and minimal improvements in negative
symptoms. Patients receiving typical antipsychotics
have shown a high rate of substance use, and
one study reported an increase in the rate of
smoking in patients treated with haloperidol.
Among the atypical, or novel antipsychotic
drugs, clozapine appears to be the most promising
so far for schizophrenic patients with comorbid
substance abuse. Initial case report studies
and retrospective surveys have indicated decrease
in substance abuse, cocaine cravings, and smoking
among schizophrenic patients. A naturalistic
prospective study[31] of 151 treatment-refractory
dual-diagnosis patients, including 36 treated
with clozapine, showed that 79% of clozapine
treated patients had remission of their alcohol
abuse compared with only 33% of those treated
with typical antipsychotics. In that same sample,
6/9 (67%) of those who used cannabis improved
on clozapine compared with 12/37 (32%) for those
treated with typical neuroleptics.
There is scant evidence for other novel antipsychotics.
One study reported decrease in cocaine craving
in patients with schizophrenia and cocaine use
while on risperidone. On the other hand, a 1-year
follow-up for patients treated with either risperidone
or clozapine showed abstinence rate of 54% (n
= 24) in those treated with clozapine and 12.5%
(n = 8) of those treated with risperidone.[32]
One open-label study reported improved substance
use outcome for patients treated with olanzapine,
and one open-label study reported a decrease
in stimulant craving for patients treated with
quetiapine. The potential role of adjunctive
medications to help decreasing alcohol and other
substance was also discussed.[28]
There are no published randomized controlled
trials to date in this population. The need
for effective interventions to treat cannabis
and other substance abuse among patients with
schizophrenia is highlighted by the early development
of cannabis abuse among these patients and its
impact on delaying treatment interventions and
the overall negative outcome.
Fluoxetine for Comorbid MDD/Cannabis Dependence
Jack R. Cornelius, MD, MPH,[33]
Professor of Psychiatry, University of Pittsburgh,
discussed the role of fluoxetine in the treatment
of adolescents with cannabis and alcohol use
disorders. He reviewed the only available acute
treatment and long-term follow-up pilot study
for this comorbidity. Studies evaluating the
efficacy of psychotropic medications in comorbid
major depression and cannabis or other substance
dependence are still few and mostly conducted
in adult populations. There are no such studies
published to date for adolescents or young adults.
It is hypothesized that low serotonergic functioning
underlies major depressive disorder, suicidal
behavior, and alcohol and substance use disorders.
Thus, medications that enhance serotonergic
functions, such as the serotonin reuptake inhibitors,
may be helpful for these conditions.[34]
In a double-blind, placebo-controlled study
of 51 adult patients with severe major depression
and comorbid alcohol dependence, fluoxetine
(20-40 mg/day) was found to decrease alcohol
use and depressive symptoms compared with placebo.[34]
Fluoxetine was also found to have an advantage
over placebo in decreasing the number of cannabis
use days, and on cumulative number of marijuana
cigarettes smoked among patients in that study
who also were marijuana abusers. The number
of days of cannabis use was 5 times higher in
the placebo group than in the fluoxetine-treated
group.[35]
Marijuana is the most frequent drug of abuse
among treatment-seeking adolescents, and comorbidity
with major depression is estimated at 15%. Relapse
apparently occurs rapidly in adolescents. A
study of 59 patients reported that two thirds
relapsed within 6 months, with median time to
relapse occurring within 2 months of discharge
from treatment. The most cited reasons for relapse
include social pressure, withdrawal, and negative
affect. Major depressive disorder was also found
to be a predictor of relapse to alcohol use
among adolescents.[36]
Limited pharmacologic treatment options are
available for adolescents with comorbid major
depression and cannabis or any other substance
abuse. There are no published randomized, placebo-controlled
trials to date in this population. Fluoxetine
is the only antidepressant approved by the FDA
to be used in adolescents.[37] Dr.
Cornelius reviewed the only long-term pilot
study of the efficacy of fluoxetine on alcohol
and cannabis use in adolescents (ages 13-19
years) with comorbid major depression and alcohol
use disorders, half of whom also had cannabis
dependence.[38] During the acute
treatment phase, patients were given fluoxetine
up to 20 mg and evaluated 8 times over a 3-month
period. There was significant improvement during
the acute treatment phase. Depressive symptoms
remitted (average Hamilton Rating Scale score
decreased from 25.6 at baseline to 6.4) over
the study period. There was also significant
decrease in the quantity (6.7 to 3.7 drinks
per drinking day) and frequency (2.6 to 1.5
drinking day per week) of drinking and a significant
decrease in the number of DSM-IV criteria for
cannabis dependence (from 5 to 2). Of the 13
subjects, 10 were followed long term in naturalistic
treatment for 1, 3, and 5 years.
Follow-up at 1, 3, and 5 years showed that
the number of adolescents who did not meet any
alcohol use diagnoses substantially increased,
from 0 (at baseline, 9 had alcohol dependence,
and 1 had an alcohol abuse diagnosis) to 5,
6, and 6, respectively. Five subjects had cannabis
dependence at baseline, which decreased to 4
at 1 year, 3 at 3 years, and 0 at 5 years. On
the other hand, those who were free from major
depressive disorders at follow-up were 3 at
1 year, 2 at 3 years, and 4 at 5 years. Thus,
there was more noticeable improvement for the
alcohol and cannabis use disorders than the
major depressive disorder. Furthermore, despite
periodic depressive symptoms, these patients
had particularly good functional outcome. At
the time of the last follow-up, 3 were enrolled
in graduate school, 6 were fully employed, and
2 had part-time employment.
Overall, the acute study showed that fluoxetine
was helpful in decreasing depressive symptoms
as well as alcohol and cannabis use. There was
no associated increase in reports of suicidal
behavior in these patients. The long-term (5-year
follow-up) outcome in this sample of adolescents
with comorbid major depression and alcohol and
marijuana use disorders appears to be good for
the alcohol and cannabis use, while the major
depressive disorder outcome may be less favorable.
In summary, there is still little empirically
based information to guide clinicians in the
treatment of most comorbid psychiatric and substance
use disorders, and more research is needed in
this area. Medication of choice should have
safe adverse-events profile, should be long-acting,
and should be associated with less abuse liability.
The &Silent& Dual Diagnosis: Tobacco
Addiction and Psychiatric Disorders
Tobacco smoking among patients with psychiatric
disorders is a significant public health problem,
with major toll on morbidity and mortality among
this population. Mental health professionals
and psychiatrists in general have been, to a
large extent, absent in addressing this problem.
Douglas Ziedonis, MD, MPH,[39] Professor
& Director, Division of Addiction Psychiatry,
UMDNJ Robert Wood Johnson Medical School, in
his presentation entitled &Psychiatrists
Should Take a Lead in Addressing Tobacco: Clinical,
Program, & System Perspectives,& discussed
the important role that psychiatrists and mental
health professionals should assume in addressing
this problem.
Psychiatric patients have a very high rate
of tobacco smoking. Individuals with a current
psychiatric disorder consume a staggering 44%
of all cigarettes consumed in the United States.
This has an estimated cost of $256 billion.[39]
Three quarters of patients in substance use
treatment and in mental health programs smoke
cigarettes. Complications of cigarette smoking
are major causes of morbidity and mortality
among these patients. Public health interventions
over the past 40 years have been very effective
in reducing smoking for most of the general
population except for those with mental illness.
There is an immediate need to provide more treatment
and to do more research to enhance our understanding
of factors related to nicotine dependence to
provide more effective treatment.
Dr. Zeidonis discussed that barriers to addressing
smoking are present at multiple levels. These
include provider, patient, a
concerns about exacerbation of psychiatric symptoms
with smoking cessation, and concerns about interactions
with psychotropic medications. Further barriers
to treatment implementation include lack of
staff training, and the fact that tobacco treatment
medications are usually not covered by health
insurance and patients are unable to afford
the cost of over-the-counter preparations. Stigma,
rationalization, minimization of the problem,
and misinformation or lack of information about
the health implications of nicotine dependence
are additional major barriers to addressing
smoking in this population.
Dr. Zeidonis suggested change must be implemented
at multiple levels by addressing clinical, program,
and system issues. For example, at the clinical
levels there is a need to implement effective
screening, assessment, and treatment strategies.
Staff training and quality improvement strategies
could be implemented at the programmatic levels,
and collaboration and networking may be undertaken
at the system levels to create prevention and
treatment programs. It is important to identify
the barriers for change and also identify the
innovations in the field.
It is important that all psychiatrists, not
just specialists, be involved in addressing
nicotine dependence among individuals with mental
disorders. Recommended steps for implementing
change at the program levels include raising
awareness of the need to address tobacco use
among this population, acknowledging the challenge,
establishing a leadership group and commitment
to change, and creating a plan for change and
an implementation timeline. Steps also include
staff training, promoting integrating tobacco
treatment into mental health and addiction setting,
and providing treatment and recovery assistance
for interested nicotine dependent staff. Tobacco
issues should be incorporated into the patient
education curriculum. Further steps include
providing on site Nicotine Anonymous meetings
and establishing ongoing communication with
other self-help recovery groups and other professional
and referral resources, and developing tobacco
One effective approach to treatment is to employ
motivation-based intervention strategies with
focus on recovery and wellness. This approach
allows the health professional to meet the patient
where he or she is and is more effective in
reducing resistance. There are a number of programs
around the country that address smoking among
psychiatric patients with specific disorders
such as PTSD, depression, schizophrenia, and
other addictions. Addressing tobacco addiction
in mental health and addiction treatment settings
with emphasis on both prevention and treatment
is overdue. Motivation-based approaches and
effective nicotine trea
however, program and system changes are critical
to the broad-based success of a model program.
The neurobiological links between smoking and
mental disorders, along with some emerging treatment
implications, were discussed by Nora D. Volkow,
MD,[40] Director, National Institute
on Drug Abuse. Dr Volkow emphasized that cigarette
smoking is implicated in at least 400,000 deaths
annually, and smoking is the single largest
preventable source of morbidity and mortality
in the United States. Twenty three percent of
American adults are smokers, and smoking typically
begins in adolescence.
Nicotine dependence is a drug addiction. Nicotine
has similar effects on the dopamine pathway
in the brain to those of other drugs such as
amphetamines, or natural rewards such as food
and sex. Nicotine causes increase in dopamine
and activation of the reward pathways, leading
to behavioral reinforcement and addiction. Nicotinic
receptors regulate dopamine release in the central
nervous system. Nicotinic acetylcholine receptors
(nAChRs), especially subunits (alpha4beta2 and
alpha7), have the highest concentration in the
central nervous system.[41] Experimental
studies with beta2 subunit &knockout&
mice showed that the beta2-containing neuronal
nicotinic acetylcholine receptor is involved
in mediating the reinforcing properties of nicotine.[42]
Cigarette smoking leads to widespread effects
on nicotinic receptors in the brain. Studies
have demonstrated that more than 50% of nicotine
receptors are occupied at nicotine levels achieved
by smokers when smoking a cigarette.
Addictive disorders often coexist with mental
disorders. While smoking rate in the general
population is 23%, much higher figures have
been reported for individuals with psychiatric
disorders, including 90% in alcoholism, 90%
in other addictions, 85% in schizophrenia, and
80% in depression. Thus, individuals with mental
disorders are at increased risk for nicotine
and other addictive disorders.
Drug abuse, alcoholism, and other addictions
mainly develop during adolescence and childhood.
There may be differential vulnerability to drug
abuse of the adolescent brain. There is experimental
evidence demonstrating that the adolescent brain
responds differently to nicotine than the adult
brain. Pre-adolescents and animals treated with
nicotine display increase in nicotine self-administration,
and also have demonstrated a significant increase
in nicotine receptors, including the beta2 subunits
linked to the reinforcing properties of nicotine.
Furthermore, there may be complex interactions
between nicotine use and some psychiatric conditions.
Patients with schizophrenia have fewer alpha7
nicotinic receptors in the hippocampus.[43]
Nicotine normalizes a sensory gating abnormality
P50 inhibitory deficit, found in most schizophrenics
and 50% of their first-degree relatives,[44]
and nicotine appears to improve concentration
among individuals with schizophrenia. A large
follow-up study found that smokers were at greater
risk to develop schizophrenia, with adjusted
relative risk of 1.94 (CI 1.05-3.58). The number
of cigarettes smoked was significantly associated
with the development of schizophrenia, and increased
risk for hospitalization for schizophrenia increased
with increased number of cigarettes smoked.[45]
Neurobiological links were also reported for
the relationship between depression and smoking.
Studies have shown that smokers have a 30% to
40% reduction in their brain monoamine oxidase
(MAO). MAO inhibitors are effective antidepressants,
and depressed patients may therefore be prone
to smoking as smoking is likely to reduce depressive
symptoms.[46,47] Individuals with
depression have more difficulty quitting smoking.
For example, women with depression have increased
depression symptoms subsequent to smoking cessation
and experience greater difficulty maintaining
early abstinence than nondepressed women.[48]
A number of treatments are currently available
for nicotine dependence, including nicotine
replacement therapy, bupropion, and MAO inhibitors.
MAO B inhibition may also be helpful in smoking
cessation.[49] Future directions
in treatment may include a number of options
such as the use of vaccines, cannabinoid antagonists
such as rimonabant, and inhibitors of nicotine
metabolism such as methoxsalen.
In conclusion, it is likely that clinicians
will confront the challenges posed by dual-diagnosis
patients, given the large number of these patients
using the healthcare system. As the results
of clinical studies are translated into clinical
practice, perhaps the future will provide some
consensus on best treatments for the highly
complex condition of comorbid substance abuse
and psychiatric disorder.
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