Chiaramente, ogni formato ha i propri vantaggi e svantaggi comprare doxycycline senza ricetta per effettuare un acquisto, non è necessario fornire la prescrizione medica.
C: itools wms tandf-journals 3651626 workingfolder ujhy_a_707156.dvi
American Journal of Clinical Hypnosis
, 55: 272–290, 2013Copyright American Society of Clinical HypnosisISSN: 0002-9157 print / 2160-0562 onlineDOI: 10.1080/00029157.2012.707156
Treating Depression With Antidepressants: Drug-Placebo
Efficacy Debates Limit Broader Considerations
Private Practice, Fallbrook, California, USA
The core issue regarding antidepressants for many clinicians is whether they perform significantly bet-ter than placebos. However, this article suggests eight additional concerns beyond drug efficacy aloneto consider regarding antidepressants including: (1) formulating only a one-dimensional, biologicalview of depression; (2) defining the client's role as passive in treatment; (3) economic corruptionof the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data thatconfuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drugside-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypno-sis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressantsas a primary form of treatment.
depression, drugs, medications, psychotherapy
On February 19, 2012, the popular American television newsmagazine program60 Minutes
aired a segment called "Treating Depression." Correspondent Leslie Stahlopened the segment by stating, "The medical community is at war, battling over thescientific research and writings of a psychologist named Irving Kirsch. The fighting isabout antidepressants, and Kirsch's questioning of whether they work." Kirsch appearedon the segment to discuss his controversial research findings suggesting antidepressantmedications are little more effective than placebos. He said:
The difference between the effect of a placebo and the effect of an antidepressant is minimal for mostpeople. . .
People get better when they take the drug, but it's not
the chemical ingredients of thedrug that are making them better. It's largely the placebo effect.
Even before the 60 Minutes
broadcast, largely in reaction to Kirsch's controver-
sial 2010 book, The Emperor's New Drugs: Exploding the Antidepressant Myth
andother similarly themed books (Barber, 2008; Healy, 2004; Peterson, 2009; Whitaker,2011), Kirsch's research has, indeed, triggered a war with nothing less at stake thanhow depression sufferers may be treated in the future. Following the 60 Minutes
piece,however, the argument escalated sharply as greater numbers of people jumped into the
Address correspondence to Michael D. Yapko, Ph.D., PO Box 487, Fallbrook, CA 92088-0487, USA. E-mail:
CONCERNS ABOUT ANTIDEPRESSANTS
debate and voiced their opinions. Kirsch has been both glorified and vilified by a widearray of experts writing in popular media outlets such as Medscape
, Psychology Today
,The New York Times
, The Huffington Post
, and many others as well. As of thiswriting, a simple Google search of the key words "Kirsch" and "antidepressants" yieldedover 75,000 results. If newspaper and magazine articles, letters to the editor, or blogs onwebsites are any indication, the general public was every bit as loud and mixed in theirreactions to Kirsch's conclusions as were the professionals. Did the 60 Minutes
pieceprovide anything beyond the mere provocation of a highly emotional debate betweenthose who pledge their allegiance to antidepressants as effective agents of treatmentand those who view them as little more than a deceptive product of greedy, lyingpharmaceutical companies that sell hope to the hopeless? It is probably of no surprisethat advocates of antidepressants continue to be advocates, and critics continue to becritics.
When the mental health profession itself is so divided over the merits of
antidepressants, and armies of prestigious experts line up on both sides of the treat-ment battlefield armed with seemingly credible data supporting their position, how isit possible to evolve any realistic measure of clarity or certainty about them? Howshould professionals, especially those with a substantial interest in hypnosis, viewthe salient issues regarding antidepressants? An in-depth knowledge of hypnosis cer-tainly highlights the roles of belief and expectancy in generating significant treatmentresponses with both antidepressants and psychotherapy, but the primary questions raisedby Kirsch's research concern just how far belief and expectancy go in helping depres-sion sufferers receiving treatment with antidepressants. The core issue concerning thoseembroiled in the controversy is whether antidepressants perform significantly better thanplacebos (Bloom, 2010; Kirsch, 2010; Kirsch et al., 2008; Kramer, 2011).
Kirsch's extensive background in hypnosis affords him a unique vantage point
from which to see the salient issues. As a frequent and important contributor to thehypnosis literature and a widely acknowledged advocate of the sociocognitive perspec-tive of hypnosis (Lynn & Green, 2011; Lynn & Kirsch, 2006), Kirsch's long-termresearch on placebo effects and his insightful framing of hypnotic suggestions as "non-deceptive placebos" (Kirsch, 1994, 2006) have had a significant impact on the field.
Psychologist John Kihlstrom, however, sensibly cautioned against identifying hypnosiswith placebo because hypnosis should be considered an active psychological treat-ment whereas placebos are inert (2012). He added, "In addition to hypnosis being anactive treatment, allowing it to be lumped in with placebos is a sure ticket to profes-sional dismissal of hypnosis for the simple reason that physicians and other therapiststhink of placebos as a nuisance to be eliminated. That's why we do placebo-controlledtrials to get rid of placebo effects" (Kihlstrom, personal communication, May 30,2012).
Despite different conceptualizations of hypnosis and its relationship to placebo
effects, Kirsch is more aware than most of the power of belief systems to alter both
physiology and subjective phenomenology (Kirsch, 1990, 2001, 2010). Does that mean,however, that he is more likely to be correct in his assertion that "Depression is a seriousproblem, but drugs are not the answer. In the long run, psychotherapy is both cheaperand more effective, even for very serious levels of depression" (Kirsch, 2010, p. 177)?As the debate noisily continues, the answer is far from clear.
Hypnosis, Placebos, and Antidepressants
It can credibly be argued that hypnosis in and of itself cures nothing
. Rather, it is whatoccurs during
hypnosis that has potential therapeutic value (Yapko, 2012). Suggestionsmay stimulate new cognitive, affective, sensory, and other associations in the client'ssubjective experience. How exactly a suggestion delivered to an individual who isfocused and attentive can stimulate often dramatic responses on multiple levels is stillbeing investigated, but the fact that measurable effects arise in response to suggestionrepresents the heart and soul of hypnosis. Suggestions can take many different forms,and as the placebo research makes clear, some of these are disguised as inert pills, shamsurgeries, and fake procedures (Harris & de Jong, 2011).
Depression is a disorder that has been shown to be highly responsive to placebo inter-
ventions (Buck, 2012; Moncrieff, 2008). What exactly does this observation tell us?It may tell us many things, but one especially plausible interpretation is that it sug-gests depression is largely a disorder of perspective
. It helps explain why there are somany different forms of treatment, each introducing some suggested shift of perspec-tive, that claim to have a significant therapeutic effect. These include widely disparatepsychotherapies that may focus primarily on cognition or affect, the individual or thefamily, the person's past or the person's present, and so forth. They also include widelydisparate drug regimens ranging from tranquilizers to stimulants, serotonin enhancersto serotonin depleters, and so forth (Bremner, 2008; Kirsch, 2010; Yapko, 2009). Whendepression is so highly responsive to virtually opposite types of interventions, the dif-ficulty is in determining how much is the treatment itself versus how much it is theindividual responding to the treatment that ultimately shapes treatment response. In thisrespect, Kirsch is conservative in his recommendation that non-chemical approacheswith no potentially deleterious drug side-effects be considered the first-line treatmentapproach (2010). Hypnosis as a vehicle for amplifying the merits of positive expectan-cies and encouraging an active treatment response is a sensible and humane treatmentchoice on this basis (Alladin, 2006, 2010; Yapko, 1992, 2001a, 2010a, 2010b).
Is it Time to Close the Barn Door?
For many, the fact of the widespread use of antidepressants has made it seem unnecessaryto question their merits; after all, what's the point of questioning something already sodeeply woven into the fabric of our society in general and mental health profession in
CONCERNS ABOUT ANTIDEPRESSANTS
particular? It seems too much like questioning whether the barn door should be closednow that the horse has already escaped.
Questioning the merits of antidepressants is necessary, however. Given their current
popularity as the second most commonly prescribed drug in the United States (behindcholesterol-lowering medications) with more than $11 billion in sales in 2010 (Smith,2012), and the still rising rates of depression around the world, increasing the numberof new potential consumers (World Health Organization, 2002), it is imperative that wehave a more detailed consideration of just how these drugs should be prescribed andfor whom. There is still time to reconsider the narrow perspective that depression is adisease requiring medication, and close enough barn doors to prevent more horses fromescaping.
Many clinicians encourage taking medications or at least seeking medication evalu-
ations for their depressed clients as standard procedure, apparently assuming that drugsare necessary and the primary intervention, while psychotherapy is merely secondary.
Many people are prescribed drugs as the sole form of intervention, despite expert recom-mendations for so-called combined treatments of medication and psychotherapy (Thase,2012). In fact, nearly 80% of antidepressant prescriptions are written by physicians whoare not psychiatrists, and only about 20% of patients on antidepressants also receivedpsychotherapy (Mark, Levit, & Buck, 2009; Olfson & Marcus, 2009). As a clinicianwho has specialized in the non-pharmacological treatment of depression sufferers whohas heavily emphasized the merits of active psychotherapies and hypnosis in treatment,and the author of numerous well-researched articles and books on these subjects (Yapko,2001a, 2001b, 2001c, 2006, 2008, 2010b), I have unequivocally and unapologeticallytaken a critical view of antidepressants. However, I have done so for reasons other thanone might expect in light of the current debate about the efficacy of antidepressants incomparison to placebos. The issues are more complex and varied than only therapeuticefficacy, and the problem of how to think about depression and its treatment is moremulti-dimensional than many seem to think. Clinicians would benefit from knowing thatthere is much more to consider than only whether the drug "works." There are manyother levels of consideration that influence treatment response and these can providea fuller view of the larger context in which drugs are utilized. Beyond antidepressantefficacy relative to placebo effects, there are eight other factors I address here in theform of "concerns" that can help inform clinicians' perspectives about the use ofantidepressants.
Concern #1: The One-Dimensional Nature of a Purely Biological Perspective
What causes depression? How one answers this fundamental question is the single mostimportant determinant of how one will design and deliver treatment as well as howone will respond to the data and divergent positions of experts. Is depression causedby genetics? A biochemical imbalance in the brain? Psychosocial stressors? Cognitive
distortions? A lack of environmental and social rewards? Social inequities? Culturaland/
or familial influences? Dietary issues? A lack of physical exercise?
Even just a cursory review of the clinical and research literature provides substantive
evidence that each
of the factors above, as well as many others not listed, play signif-icant roles in the onset and course of depression (Cozolino, 2006; Goodman & Gotlib,2002; Nolen-Hoeksema, 2000; Pettit & Joiner, 2006; Reblin & Uchino, 2008; Thomas& Peterson, 2003; Yapko, 1997, 1999, 2009). Thus, it seems the best and most realisticanswer to the question of what causes depression is that depression is caused by many
contributing factors that will vary in degree across individuals.
Biology run amok has been overstated as the principal causal factor in depression
when evidence for this viewpoint is equivocal at best and psychological
fac-tors have been shown to play an even greater role in its onset and course (Healy, 2004;Lacasse & Leo, 2005; Scott, 2006; Yapko 1997, 2010b). To simply medicate an individ-ual as though he or she is depressed in isolation, excluding others from treatment whomay affect and be affected by the client's depression, ignores the entire social dimensionof depression to the detriment of the client (Yapko, 2009). Thus, prescribing medicationalone is too one-dimensionally biological a treatment, an unambiguous under-treatmentthat may help explain the higher rate of relapse associated with purely pharmacolog-ical approaches (Alladin, 2006; Beck, personal communication, December 15, 1990).
Clinicians can better view and treat depression from a multi- dimensional perspective,especially using hypnosis as a means of encouraging the client to adopt the empoweringperspective that, "I am more than my biology."
Concern #2: The Passive Definition of the Client's Role
Depression is a disorder built on a foundation of passivity. "Why bother?" may wellbe the unofficial motto of depression. It is not a coincidence that the therapies withthe greatest empirical support all emphasize taking purposeful and sensible action
intreatment (Detweiler-Bedell & Whisman, 2005; Jacobson, Martell, & Dimidjian, 2001;Yapko, 2010b). To merely prescribe an antidepressant as a sole form of intervention isto impart the terribly unhelpful message: You don't have to change your life, you don'thave to learn any new skills; you just have to take your medication on time. The problemisn't in your outlook or circumstances—it's in your brain chemistry
Antidepressants don't directly cause people to be passive. Depression itself does that
quite well. But antidepressants, when prescribed as a sole intervention, inarguably dodirectly define people's role in treatment
as passive: the client is literally instructed totake the drug and, with high hopes, patiently wait for the drug to "work." For those well-informed clinicians who strive to empower people to be proactive in managing life skill-fully, medication as a sole form of passive treatment simply isn't the best means to do so.
Clinicians would do better to encourage the client to be an active partner in a
collaborative treatment process. They can do so by providing active psychotherapies
CONCERNS ABOUT ANTIDEPRESSANTS
which may best utilize hypnosis as a means of facilitating the client's acquisition ofskills known to reduce and even prevent
depression (Alladin, 2006, Muñoz, Beardslee,& Leykin, 2012; Yapko, 1997, 2001a, 2009). Furthermore, beyond the formal therapysession itself, the clinician can offer skill-building homework which encourages experi-menting with shifting perceptions, testing beliefs, and trying new behaviors (Alladin &Alibhai, 2007; Lankton, 2006; Yapko, 2001a, 2010b). There is substantial evidence thatthe use of active homework assignments enhances therapy results (Detweiler-Bedell &Whisman, 2005). These can be "seeded" during hypnosis, preparing the client to act onthe recommended assignments (Zeig, 1990).
Concern #3: Economic Corruption and Undue Influence of Pharmaceutical
Companies on Data Dissemination
Two recent reports published in the Journal of the American Medical Association(JAMA)
raised concerns about how drug companies influence the interpretation and pub-lication of medical research (Psaty & Kronmal, 2008; Ross, Hill, Egilman, & Krumholz,2008). The reports provided evidence that drug manufacturers have paid academic sci-entists to take credit for research articles prepared by company-hired medical writers, apractice called ghostwriting.
This deceptive practice is not uncommon, according to JAMA's
editors. In an edito-
rial in the same issue, they urge strict reforms, including a ghostwriting crackdown andrequiring all authors to spell out their specific roles in the research and reporting. Dr.
Catherine DeAngelis, JAMA's
former editor-in-chief, in a blistering editorial, wrote,"The manipulation is disgusting. I just didn't realize the extent. . .
We're the ones whohave allowed this to happen. Now we've got to make it stop" (2008, p. 1833).
The problem is much bigger than ghostwriting, however. As an organization, the
American Psychiatric Association receives substantial funding from the pharmaceu-tical industry. The Association produces DSM
and is currently in the contentiousprocess of preparing DSM-V
; 100% of the individuals on DSM-V
panels for bothschizophrenia/
psychotic disorders and mood disorders have financial ties to the drugindustry (e.g., speaker's bureau, receiving honoraria, on the board of a drug company).
Researchers studying financial conflict of interest in clinical trials of psychiatric medi-cations found that among the 162 randomized, double-blind, placebo-controlled studies(RCTs) reviewed: (1) authors who reported an association with a drug company were4.9 times more likely to report positive results than those who did not report such anassociation; (2) the severity of adverse effects of medication was not reported in 27.1%of the studies reviewed; and (3) withdrawal rates from the study because of adverseeffects was not reported in 47.4% of RCT studies (Cosgrove, 2010).
Clinicians and researchers must understand the potential conflicts of interest that
may arise with drug company funding of their research or clinical practices. They mustactively resist those self-serving external forces that attempt to control or manipulate
how one does research or provides treatment as well as the possible temptation fromfinancial incentives to misrepresent findings. Readers of research must likewise be awareof the potential for misrepresentation and maintain a healthy skepticism of findings whenthere may be a conflict of interest. Reading the fine print regarding funding is advised.
Concern #4: Pseudoscientific False Advertising
The United States is one of only two countries that allow direct-to-consumer advertising,the other being New Zealand (Weil, 2012). Virtually all Americans have been exposedto the ongoing blizzard of ads for antidepressants which declare that "depression may
becaused by a chemical imbalance and (our drug) corrects this imbalance." The "shortageof serotonin" is a heavily touted hypothesis regarding the cause of depression that haslittle empirical basis but a growing mass of contradictory evidence (Carlat, 2010; Weil,2012). But, the heavy repetition of the drug manufacturer's creed that "depression iscaused by a biochemical imbalance in the brain" means people may hear it so often thatthey stop thinking critically about it and accept it as established fact (Peterson, 2009).
It is far from that. The decline of the serotonergic hypothesis of depression has beendescribed in many places (Angell, 2011; Scott, 2006; Whitaker 2011), but was especiallywell captured in an article in the science magazine Seed
(Lehrer, 2006, p. 63):
For the last 40 years, medical science has operated on the understanding that depression is causedby the lack of serotonin . .
the theory is appealingly simple: Sadness is simply a shortage of chem-ical happiness. The typical antidepressant—like Prozac or Zoloft—works by increasing the brain'saccess to serotonin. If depression is a hunger for neurotransmitter, then these little pills fill us up.
Unfortunately, the serotonergic hypothesis is mostly wrong. After all, within hours of swallowing anantidepressant, the brain is flushed with excess serotonin. Yet, nothing happens; the patient is no lessdepressed. Weeks pass drearily by. Finally, after a month or two of this agony, the torpor begins tolift. But why the delay? . .
a range of antidepressants trigger a molecular pathway that has little, ifanything, to do with serotonin. Instead this chemical cascade leads to an increase in the production ofa class of proteins known as trophic factors. Trophic factors make neurons grow . .
Despite the suggestion that a biochemical anomaly causes depression, a uni-
directional process, life experience itself also changes biochemistry, reflecting a bi-directional even systemic process. The current neuroscience highlights the fact that psy-chotherapy changes brains
, just as medication does, although in different ways (Siegel,2007). Neuroplasticity refers to the changes in the brain as a result of experience. In fas-cinating descriptions of examples of neuroplasticity in his book, The Brain That ChangesItself
(2007), neuroscientist Norman Doidge described mechanisms and consequencesof neuroplasticity. The use of experiential processes such as hypnosis and mindfulnessappear to encourage neurogenesis and neuroplasticity (Halsband, Mueller, Hinterberger,& Strickner, 2009; Rossi, 2003; Simpkins & Simpkins, 2010; Yapko, 2011).
Studies of brain changes as a result of psychotherapy reinforce the growing aware-
ness for the phenomenon of neuroplasticity. In one study at UCLA (Brody et al.,
CONCERNS ABOUT ANTIDEPRESSANTS
2001), comparing brain changes in a 12-week trial of antidepressants to interpersonalpsychotherapy, the magnitude of brain changes were highly similar. In another studyconducted in England (Martin, Martin, Rai, Richardson, & Royall, 2001), interpersonaltherapy compared to the antidepressant Effexor yielded similar results. These studiesshowed that in response to psychotherapy alone, patients demonstrated decreases in pre-frontal cortex activity, increased activity of the cingulated gyrus, and increased activityof the caudate nucleus. Such studies naturally raise more questions than they answer.
But, every clinician must consider that each suggestion, delivered in or out of hypnosis,has potential effects on multiple levels, including neurological ones. Drugs aren't theonly agents capable of neurological influence.
Clinicians can resist being swayed by misleading advertising by staying current with
the scientific literature. More than that, they can help lobby against direct-to-consumeradvertising in general and misleading advertising in particular (Angell, 2005; Healy,2004; Weil, 2012).
Concern #5: Conflicting Data That Confuses Almost Everyone
It is all too common in the drug industry for a drug to be approved by America's Foodand Drug Administration (FDA) and brought to market with the implicit assurance thatthe drug is safe for consumers only for the drug to later be found unsafe and then pulledfrom the market after lives are lost or harmed. The antidepressant Serzone, as just oneexample, was popularly prescribed then pulled from the market when it was shown tocause liver damage that resulted in some fatalities.
This special issue of the American Journal of Clinical Hypnosis
came about in attempt
to shed light on this very issue: Whose data do we believe when credible data conflictwith each other? If professionals find it hard to answer this question, how must typicalconsumers feel?
Consider as an example the issue of antidepressant safety for children: In the April 18,
2007, issue of JAMA
, researchers (Bridge et al.) claimed that the suicide threat fromSSRIs for young people was exaggerated and recommended that the "black box" warn-ing be lifted. (A "black box" warning is the strongest warning placed on medicationpackaging. In the case of antidepressants, a warning was given about the increased riskof suicidal ideation and behavior in children and young adults receiving antidepressants.)On May 2, 2007, just 2 weeks later, the FDA required drug manufacturers to expand
theirblack box warnings! The original warning was for children and adolescents up to age 18.
It is now for young adults up to age 24, as well (Friedman & Leon, 2007). In a newercontradictory study, researchers concluded that the antidepressants were indeed safe anddid not increase suicidal ideation or increase the risk for suicidality (Gibbons, Brown,Hur, Davis, & Mann, 2012).
Should pediatricians feel comfortable prescribing these drugs to children when
the long-term effects (i.e., neurological, behavioral, social, developmental) are largely
unknown? Should parents feel comfortable having their children on antidepressantswhen it is unclear what the actual risks to them might be? Drugs are not the only effec-tive means of helping depressed young people nor should they necessarily be prescribedas the treatment of choice.
As another example of contradictory expert feedback, consider the hotly debated issue
of how long the patient should be on antidepressant medication: Some experts say 1 year,some say 5 years, some say forever
despite the fact that no one has been on these drugsfor life in order to provide any empirical evidence for such a long-term recommenda-tion (Banov, 2010). The oldest of the newer generation antidepressants, Prozac, is only24 years old. Most drugs are much younger than that. What is personal bias and what isscience in making so important a recommendation as to how long one should expect tobe on a medication?
One additional example of contradictory expert recommendations concerns the safety
of antidepressant usage by women who are pregnant or may become pregnant. Someresearch has suggested there is no significant risk from taking antidepressants to eitherthe mother or fetus, while other research has suggested a substantial risk, includingcardiopulmonary issues and birth defects (see Rosenquist, this issue, for details).
Clinicians can better recognize the subjective biases of "experts" in areas where no
such expertise can exist, simply because conclusive data aren't available yet.
Concern #6: Drugs Are Over Prescribed, and Paradoxically, Under Prescribed
Despite the overall increase in the number of people seeking help for depression, esti-mates are that only half of depressed people receive any
form of treatment, and onlyabout half of these receive adequate treatment (Kessler et al., 2003; Lynn, Malakataris,Condon, Maxwell, & Cleere, 2012). In this sense, the drugs are under-prescribed.
At the same time, there are some doctors eager and willing to write a prescription as
soon as they discover their patient faces some stressor, such as the death of a loved one,apparently assuming the person will need the drug to cope. In a new book, Coming of Ageon Zoloft
(2012), the author, Katherine Sharpe, describes how she went to her collegehealth center with a bad case of homesickness. There she had only a 20-minute appoint-ment during which she received a prescription for the antidepressant Zoloft—a drug shewould take for the next 10 years
. It may have been a well-intentioned gesture, or it mayhave been the result of an overcrowded, understaffed college health center. Either waythe net effect is to pathologize normal responses to stressful circumstances and disem-power the person from managing her responses to difficult but common life challenges.
Furthermore, in this era of the highly questionable practice of direct-to-consumer drugadvertising, there are people impressed by the ads who brazenly ask for and actuallyreceive antidepressants for questionable reasons, ranging from the global complaint "Ijust wanna be happy," to wanting to lose weight or perform better on the job. Patientswho requested advertised drugs were more than 16 times more likely to receive one or
CONCERNS ABOUT ANTIDEPRESSANTS
more new prescriptions from their doctors than patients who did not request any drugs(Smith, 2012). In this way, these drugs are over-prescribed.
There is evidence to indicatethe proportion of inappropriate prescriptions of antidepressants is growing (Mojtabai &Olfson, 2011; Smith, 2012).
A realistic use of antidepressants has yet to develop perhaps, in part, due to the
ambiguous nature of the disorder itself. Diagnostically, there are no clear dividing linesseparating unhappiness from depression or separating degrees of depression. Thus, thedanger exists that people may see depression where it isn't, and not see it where itexists. Helping people think more realistically about depression and its treatment isa worthwhile endeavor. Toward that end, clinicians can create and participate in out-reach programs to encourage seeking help for depression (e.g., public lectures, nationaldepression screening day participation, media participation), while encouraging peopleto develop a realistic sense of what the medications can and cannot do for the client.
Concern #7: Drug Side Effects Can Be More Than Just an Irritant
In a study by Gandhi and colleagues (2003), SSRIs were the class of drug most com-monly found in adverse drug events. At the very least, side effects can reduce or preventparticipation in treatment, complicate symptoms, and thereby unintentionally serve toreinforce
depression. The fact that response to antidepressants is so variable can amplifythe client's pessimism and fuel frustration: "At present, the most effective medicationfor a given patient is identified through trial and error, a long and costly process, whichhas a negative impact on long-term outcome" (Keers, 2012, p. 319).
Individuals may stop taking the medication and resign themselves to being depressed
when they try a medication that does nothing to help them, a reflection of the lack offrustration tolerance commonly associated with depression (Moncrieff, 2008; Yapko,1997). Furthermore, a significant number of patients stop taking the antidepressantsbefore they have a chance to help because of an inability to tolerate the negative sideeffects (e.g., nausea, sedation or agitation, insomnia, headache, dizziness, fine tremor,sexual disturbance, weight gain, and bone fractures in individuals over age 50). Othersfear a physical dependence on the medications because of the well-known "discontin-uation syndrome," such as the physical discomfort associated with stopping the use ofantidepressants (Banov, 2010; Glenmullen, 2006).
The unintended effects of antidepressants go much further than transient discomforts
in the medicated individual. As Rosenquist points out in this issue, the serious unin-tended effects of medicating pregnant women may include neuro-developmental issues,increased pain reactivity, neonatal pulmonary hypertension, neonatal cardiac malforma-tions, and other potentially serious anomalies affecting the physical and mental health ofthe developing fetus and neonate.
Another unintended—and perhaps unexpected—side-effect is the ease with which
some doctors can self-medicate with antidepressants. In a survey of Michigan
psychiatrists listed by the Michigan Psychiatric Society, over 15% revealed they haveself-medicated for depression, 43% say they would do so for mild depression, 7% forsevere depression. Those who were more biologically oriented in their views and prac-tice were more likely to either self-medicate or consider doing so (Balon, 2007). Whatdoes this suggest about a presumed objectivity and clinical judgment in prescribing?
Drug manufacturers have paid out huge sums of money in lawsuit settlements for
causing a wide array of health-related problems, reinforcing the recognition that thesemedications are not innately benign no matter how well intentioned their purpose(Banov, 2010; Glenmullen, 2006; Peterson, 2009). Clinicians can highlight at everyopportunity that psychotherapy's treatment success rate matches and, in some specificways, even exceeds antidepressants without
side effects. This is one of Kirsch's primarypoints in pointing out the presence of a placebo effect in the drug treatment of depression,one that can be matched with psychotherapies that do not generate potentially hazardousside-effects (Kirsch, 2010). Well considered therapeutic interventions utilizing hypnosiscan benefit the body, mind, and mood of the depressed client (Alladin, 2012; Yapko,2001a, 2006, 2010b).
Concern #8: Ecological Concerns about Drugs
Ecological scientists have raised an unexpected concern regarding the harmful effects ofmedications on the environment: The presence of drugs in our drinking water.
Traces ofmore than 100 different pharmaceuticals, or their byproducts, were found in the drinkingwater supplies of at least 41 million Americans, including medicines for pain, infection,high cholesterol, asthma, epilepsy, mental illness, and heart problems (Donn, Mendoza,& Pritchard, 2008).
Human excretions are the major factor in spreading pharmaceuticals through the
waste stream. Drugs that are thrown away end up at landfills, where they can slowly seepinto the groundwater (Daughton, 2008). Additionally, U.S. manufacturers, includingmajor drug makers, have legally released at least 271 million pounds of pharmaceuticalsinto waterways that often provide drinking water—contamination the federal govern-ment has consistently overlooked, according to an Associated Press (AP) investigation.
The AP also found that an estimated 250 million pounds of pharmaceuticals and contam-inated packaging are thrown away each year by hospitals and long-term care facilities(Donn, 2009).
At a 2007 conference, Mary Buzby, the Director of Environmental Technology
for drug maker Merck & Co., quoted in the The Collaborative on Health and theEnvironment eNewsletter
(March 13, 2008) said:
there is genuine concern that these compounds, in the small concentrations that they're at, couldbe causing impacts to human health or to aquatic organisms. . .
There's growing concern in thescientific community, meanwhile, that certain drugs or combinations of drugs may harm humans overdecades because water, unlike most specific foods, is consumed in sizable amounts every day. . .
CONCERNS ABOUT ANTIDEPRESSANTS
Our bodies may shrug off a relatively big one-time dose, yet suffer from a smaller amount deliveredcontinuously over a half century, perhaps subtly stirring allergies or nerve damage. Pregnant women,the elderly and the very ill might be more sensitive.
Small amounts of medication have been shown to have an adverse human impact.
This includes researcher's discovery of affected human embryonic kidney cells growingtoo slowly, human blood cells showing signs of inflammation, and human breast cancercells growing too quickly (Donn, 2009).
They are also damaging wildlife; for example, male fish are being feminized,
evidenced by the anomaly of their creating egg yolk proteins, a process usuallyrestricted to females. In an article published in Environmental Science and Technology
,it was reported that elevated concentrations of commonly prescribed antidepressantswere found in the neural tissue of fish in two tested streams, Boulder Creek nearBoulder, Colorado, and Fourmile Creek near Ankeny, Iowa (Schultz et al., 2010). Theantidepressants were found in fish collected over 5 miles downstream of the locationof the wastewater discharge from water treatment plants. The scientists detected severalcommonly used antidepressants in the water, streambed sediment, as well as the braintissue of white suckers, a native fish species. Fish collected upstream from the wastewa-ter discharge did not have antidepressants present in their brain tissues. The implicationshave yet to be determined, but there is a basis for concern when water and fish arecontaminated in this way.
Though pharmaceutical sales are rising, plants that cleanse sewage or drinking water
are not currently required to remove drugs; in fact, there has been no national strategy todeal with them—no effective mandates to test, treat, or limit drug waste or even advisethe public about the potential hazards. Recently, however, government regulators arebeginning to move toward dealing with pharmaceuticals as environmental pollutants:(1) The Environmental Protection Agency (EPA) has listed some pharmaceuticals ascandidates for regulation in drinking water. The agency also has launched a survey tocheck for scores of drugs at water treatment plants across the nation; (2) The FDA hasupdated its list of waste drugs that should be flushed down the toilet, but the agency hasalso declared a goal of working toward the return of all unused medicines; and (3) TheNational Toxicology Program is conducting research to clarify how human health maybe harmed by drugs at low environmental levels (Dodd, 2009).
The unintended consequences for the environment and for human health which
depends on a healthy environment will likely yield long-term effects we can't realis-tically even imagine right now. Clinicians can provide sensible, "green" treatments inthe form of psychotherapy utilizing hypnosis. Talking doesn't pollute the environment.
Concern #9: The Arguable Therapeutic Efficacy of Antidepressants
The issue giving rise to this special issue of the American Journal of Clinical Hypnosis
regarding just how effective antidepressants really are makes all the other concerns
secondary, though still very important. If antidepressants were highly and unequivo-cally successful as safe therapeutic agents, the other concerns might seem considerablyless significant to some. Just how successful are they? We don't really know, but there isample evidence their merits have been overstated.
In January 2008, the New England Journal of Medicine
published an article (Turner,
Matthews, Linardatos, Tell, & Rosenthal, 2008) that was staggering in its implica-tions for how science is done and how the results of research studies in general andantidepressant studies in particular are published and released to both professionals andthe general public alike. The article documented the fact that research on antidepressantmedications was, for years
, published selectively, a point Kirsch alluded to in his60 Minutes
appearance. Erick Turner, himself a former reviewer for the FDA, and hiscolleagues, wrote that when a study showed a finding favorable to the drug company,it was highly likely (94% chance) to be published. But, if a study wasn't
favorable toa drug, that study was very unlikely (only a 14% chance) to be published. Studies withnegative findings were essentially hidden from view, never analyzed in order to get amore objective view of the merits of the antidepressant being tested.
One doesn't have to go very far in one's thinking to wonder why negative stud-
ies would be omitted from consideration and who benefits from such exclusion. Afterincluding these omitted data to their study of antidepressants' effectiveness, the authorsstated:
We found a bias toward the publication of positive results. Not only were positive results more likelyto be published, but studies that were not positive, in our opinion, were often published in a way thatconveyed a positive outcome. We analyzed these data in terms of the proportion of positive studiesand in terms of the effect size associated with drug treatment. Using both approaches, we found thatthe efficacy of this drug class is less than would be gleaned from an examination of the publishedliterature alone. . .
As a result of selective reporting, the published literature conveyed an effect sizenearly one third larger than the effect size derived from the FDA data. (Turner et al., 2008, p. 258)
In February, 2008, Kirsch and colleagues reported on data they had acquired from
the FDA through the Freedom of Information Act regarding the licensing of the sixmost popularly prescribed antidepressants approved between 1987 and 1999 (Prozac,Paxil, Effexor, Serzone, Zoloft, and Celexa). Their analysis of the data that led to FDAapproval of these drugs showed that these antidepressants had a minimal benefit beyonda placebo effect. The authors concluded, "Meta-analyses of ADMs have reported onlymodest benefits over placebo treatment, and when unpublished trial data are included,the benefit falls below accepted criteria for clinical significance." This was the research,in part, which gave rise to the 60 Minutes
story which, in turn, gave rise to this specialissue of the American Journal of Clinical Hypnosis
Most recently, the conflict over the efficacy of antidepressants reached new heights
in contradictory considerations in the scientific literature. The 2010 article in JAMA
by Fournier and colleagues was summarized in a MedScape
article titled, "Efficacy ofAntidepressant Medication vs. Placebo Increases With Severity of Depression" (Barclay,
CONCERNS ABOUT ANTIDEPRESSANTS
2010). The authors suggested that antidepressant efficacy was a function of the sever-ity of the depression. More recently, a contradictory article, also posted on MedScape
,boldly carried the title, "Antidepressants Work, and Depression Severity Does NotMatter" (Roy-Byrne, 2012). Do antidepressants work and are they more effective thanplacebos? The answer is still clearly yes and no.
In a remarkable study—the first of its kind—biological evidence was found to sup-
port the hypothesis that much of the therapeutic effect generated by antidepressants isattributable to the placebo effect. Dr. Aimee Hunter and her colleagues at the UCLANeuropsychiatric Institute studied the relationship between EEG changes and clinicaloutcome on patients taking Effexor and Prozac. Changes in prefrontal EEG patternswere recorded during a placebo lead-in phase, often conducted before randomization todrug treatment in clinical trials. The authors stated "Brain changes during the placebolead-in phase may confound apparent medication effects associated with clinical out-comes in medication-treated subjects. . .
Some neurophysiological changes that areassociated with endpoint antidepressant outcome reflect nonpharmacodynamic factors"(Hunter, Leuchter, Morgan, & Cook, 2006, p. 1429).
Simply put, brains changed when no active drug was administered, and these changes
predicted response to antidepressant treatment in depressed patients. Do antidepressantsprovide some benefit beyond placebo? Perhaps so, but perhaps not to the degree or in theway we may have been led to believe. The enthusiasm for antidepressants is not justifiedby the science, and routinely making them the foundation of depression treatment canbe reasonably considered a questionable practice.
Clinical Implications for Clinicians Utilizing Hypnosis
Even the strongest advocate for antidepressants must admit there are limits regardingwhat antidepressants can realistically be expected to do for someone. Antidepressantsnot only will not but cannot
teach the depressed client the kinds of personal and inter-personal skills that can empower him or her to better manage mood-related issues. To bespecific, medication cannot teach depressed individuals better problem-solving skills,more adaptive coping skills, more sophisticated social skills, better and more realisticcognitive processes, or more flexible and effective behavior. Furthermore, medicationcannot enhance one's spiritual life or help the client build a positive support network.
Finally, they cannot be used preventively to forestall a first episode's onset, unlike ther-apy and education which have great preventive potential (Muñoz et al., 2012). This isespecially important to consider given the evidence that as depression crosses genera-tions, it becomes more pervasive and also more severe (Weissman, 2005; Yapko, 1999,2009).
Thus, one immediate guideline for any clinician to adopt would be to help impart real-
istic expectations for what an antidepressant can and cannot do by avoiding the framingof depression as a medical disease needing exclusively biological treatment. This alone
would greatly influence the quality of client expectancy, a key ingredient affecting treat-ment response. Well beyond that, though, the clinician utilizing hypnosis can focus theclient on other psychological and social issues that are key ingredients of successfultherapy, such as evolving flexibility, experimenting with beliefs and perceptions, learn-ing to recognize and tolerate ambiguity, building positive social skills, and much more.
These have been described in substantial detail in previous writings (Yapko, 1997, 1999,2001a, 2006, 2008, 2009, 2010b).
Given the rising rate of depression in the United States and around the world, and theevidence that depression intensifies from one generation to the next, how this generationof clinicians thinks about depression and its treatment will have consequences that gofar beyond this discussion. The issues addressed here are complicated and there is nosingle, clear conclusion to be drawn about the merits of antidepressants.
Americans too readily look for quick solutions based on what's easiest or most conve-
nient rather than what's best. The ease with which people put powerful chemicals in theirbody on the basis of too little good research and too much exaggerated advertising is alegitimate cause for concern. Likewise, the ease with which many clinicians routinelyadvocate the use of medications without considering the range of factors presented inthis short article is also a legitimate basis for concern. There's simply too much wedon't yet know about antidepressants to embrace them enthusiastically, and there is toomuch about them we have ignored by getting sidetracked by ill-founded one-dimensionalarguments one way or the other. The concerns raised in this article can help broaden thediscussion beyond only whether the drugs work to include other important factors thateveryone in positions of authority making treatment recommendations should consider.
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