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Greg Whitehurst
Dr. Guenzel
ENC 1102, Sec #2
26 March 2013
Research Dossier: Generic vs. Brand-Name Psychoactive Medications
Dossier Introduction
In the medical field, the choice between generic and brand-name psychoactive drugs,
both by prescribing doctors and by their patients, is fueled by the question of whether or not they
truly are the same. Researching this topic has led me to find that this has been a highly
unresolved issue with compelling evidence on both sides, and that the word “same” in this
context is subject to debate itself. The generic drug market began in the 1920’s with generic
aspirin, but regulations on the efficacy of generic drugs were loose until 1962 with the passage of
the Federal Food, Drug, and Cosmetic Act. The legislation was an answer to a tragic occurrence
of birth defects across Europe due to a generic sedative on the market, and the FDA required that
all generic drugs go through human trials similar to the process for brand-name versions.
Since then, regulations have been softened, with the FDA only needing proof that the
generic drug is chemically the same, or the bioequivalent of the brand-name before it can be
introduced to the market. This raises many concerns, including whether the evaluation process of
generic drugs is rigorous enough or if they even have the same effects on patients. Although it is
important that the generic medications truly are bioequivalent, the psychology of the individual
taking the drug must be taken into account, especially in the case of drugs that alter physical
brain function. Because there are no longer tests for generic drug efficacy, this is where research
is needed: to understand if generic drugs are as effective and safe as brand-name drugs regardless
of their bioequivalency.
I believe this is a very important topic to be understood. It is estimated that up to 50% of
the United States population will suffer from at least one psychiatric disorder in their lifetime,
and at least half of those individuals will seek treatment. Many individuals are prescribed
psychoactive drugs for issues such as anxiety, depression, ADHD, or even less serious problems
such as trouble sleeping. The psychiatrists who choose to prescribe one version of the drug or the
other have a responsibility to know any potential harm generics might cause, and anyone
currently taking a prescription psychoactive drug should be informed on any potential
differences. These two groups of people would mainly benefit from this research.
After researching the topic at great length, it seems there are three sides to the issue
although they are not entirely distinct. Surveys and studies show that a significant percentage of
people do not expect generic drugs to be as effective as the brand-name versions, and
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interestingly this belief seems to actually reduce the effectiveness of the medication when
patients are switched from one to the other. This is known as the nocebo effect, and it is part of
the argument that since the difference stems from patients’ beliefs, that doctors simply need to
fully educate their patients about how generic drugs are no different than the brand-names. The
sources listed that apply to this argument are Gaudiano and Miller’s study of bipolar patients
(2007) and Roman’s 2009 survey given to patients on antipsychotics; all of the sources
referenced in this paragraph can be found in the annotated bibliography at the end of this paper.
A second viewpoint is based off of case studies that show severe relapses in patients who are
switched to generics, and this viewpoint claims that more trials and research are needed for
generic drugs because of the serious complications that sometimes occur. This view also gives
importance to manufacturing differences, and the sources for it are a meta-analysis by Borgheini
(2003), case studies reviewed by Margolese (2010), and a magazine article by Dunckley (2012).
A final argument lies somewhere in the middle, with the idea that because generics do sometimes
cause problems, this can be solved by evaluating any potential switch to generics on a case by
case basis. The sources related to this argument are journal-published studies by Bobo (2010)
and Howland (2010). I will be looking at all three sides of the issue; I hope to provide relevant
information for doctors and patients to make well-informed decisions when choosing brandname or generic medication.
Research Map
Progress
My original idea was based off Daniel Ariely’s research showing that painkillers are less
effective when people are told they are discounted versions of the normal painkillers. This study
was referenced in the non-fiction book Cheap by Ellen Ruppell Shell, and my research goal
became: How do generic or brand-name psychoactive medications affect people differently
based on their perceptions of the differing costs? This became more complex as I discovered that
most research until now has only been able look at the differences by observing individuals who
have switched from one to the other, and most do not specifically look at cost perceptions. Thus,
I had to expand my research on how the perceptions and expectations of individuals influence
efficacy.
The thesis for my research is that brand-name medications have a higher efficacy than
generic medications in treatment, but this is only because of the perceptions of the patients as
opposed to the manufacturing of the drugs. The research thus far has led me to believe that this
thesis is accurate, although my research focused more on the effects on the patients rather than
the manufacturing process. As far as I can tell, no studies trace back a generic drug to where and
how it was manufactured when there is a problem with a patient.
This research question could be easily answered if there were many controlled studies
that used a sample of individuals who were given a brand-name drug and another sample who
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were given a generic. However, these studies are extremely rare. I was able to find many sources
from scholarly journals, the internet, magazines, and newspapers. I do plan, though, to do a
survey myself asking individuals what their attitudes on generic drugs are. I have had four exams
and two quizzes in the past week, so I have not had time yet to perform this survey. It will,
though, give me a field research source that will hopefully reinforce current studies that show a
significant percentage of people feel like generics are less effective than brand-names.
Key Terms
Generic Drugs
Brand-Name Drugs
Bioequivalent
Nocebo Effect
Efficacy
Expectancy Effects
Double-Blind Studies
Timeline
2/25-3/3
2/26: Physics
Exam
3/4-3/10
Spring Break
(no school
work done)
2/27:
Research done
in the library.
4/1-4/7
4/2: Research
Rough Draft
due
4/4: Organic
Chemistry
4/8-4/14
4/9: Finish up
field research
if not
completed.
4/11 Research
Conference
3/11-3/17
3/13:
Research
done in the
library
3/15: Organic
Chemistry
Quiz
4/15-4/21
4/16: Finish
the final draft
of the
research
paper.
4/18 Research
Final Draft
3/18-3/24
3/19: Research
done in the library
3/25-3/31
3/21: Annotated
Bibliography
Rough Draft due
3/26: Annotated
Bib Final,
Physics Exam
Organic Chemistry
Exam
3/22-3/24: Miami
Trip (no school
work done)
4/22-4/28
4/25 Self
Assessment and
Portfolio Due
3/28: Create
survey for field
research.
4/29-4/30
4/29: Organic
Chemistry Final
Physics Final
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Quiz
Draft due
due
Organic Exam
Annotated Bibliography
Bobo, W., Stovall, J., Knotsman, M., Koestner, J., & Shelton, R. (2010). Converting from brandname to generic clozapine: A review of effectiveness and tolerability data. American
Journal of Health-System Pharmacy, 67(1), 27. doi: 10.2146/ajhp080595
Summary from Abstract: PURPOSE: The effectiveness and tolerability of switching patients'
therapy from brand-name to generic clozapine are reviewed. SUMMARY: Clozapine is the most
effective treatment for patients with refractory psychotic disorders and is also effective for
reducing suicidal and violent behavior in this same population. Generic versions of clozapine are
widely used. However, possible differences in pharmacokinetic profiles between branded and
generic clozapine, and the potential risks of medication changes in severely ill but stable patients,
may result in apprehension about converting from branded to generic clozapine. Articles,
abstracts, and clinical presentations that compared clinical outcomes between Clozaril (Novartis
Pharmaceuticals, East Hanover, NJ) and generic forms of clozapine in patients with primary
psychotic disorders, bipolar disorder, or related conditions were identified via a computerized
search of the medical literature. Thirteen relevant reports, mostly uncontrolled observational
studies or chart reviews, described the effects of switching from brand-name to generic clozapine
in 966 patients. The majority of patients tolerated conversion without worsening of symptoms or
adverse effects, increased intensive service utilization, or medication adjustment. Clinical
deterioration was described in a case review and in one randomized, controlled study.
CONCLUSION: Available literature supports the effectiveness and safety of generic clozapine
formulations in patients who previously were stable during treatment with brand-name clozapine.
The risk of poor outcome after conversion to a generic clozapine formulation appears to be low
but difficult to predict. Patients should be closely monitored during the first one to three months
after conversion from one formulation to another.
The authors seem to be credible as this source is from a peer-reviewed journal. They looked at a
large sample size compared to many other studies on the topic of generic and brand-name
medications, and they took this sample size from a total of thirteen separate studies. These two
factors also add to their credibility and give reason to believe they were unbiased in their
research. This article exemplifies the viewpoint that generic drugs are mostly safe but should still
be evaluated on a case by case basis.
Borgheini, G. (2003). Bioequivalence and other unresolved issues in generic drug substitution.
Clinical Therapeutics, 25(6), 1578-92.
Summary from Abstract: For the purposes of drug approval, the interchangeability of a generic
drug and the corresponding brand-name drug is based on the criterion of “essential similarity,”
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which requires that the generic drug have the same amount and type of active principle, the same
route of administration, and the same therapeutic effectiveness as the original drug, as
demonstrated by a bioequivalence study. However, bioequivalence and therapeutic effectiveness
are not necessarily the same. Objective: This review summarizes available data comparing the
bioequivalence and therapeutic efficacy of brand-name psychoactive drugs with those of the
corresponding generic products. Methods: Relevant information was identified through searches
of MEDLINE, Current Contents/Clinical Medicine, and EMBASE for English-language articles
and English abstracts of articles in other languages published between 1975 and the present. The
search terms used were generic drug, branded drug, safety, toxicity, adverse events, clinical
efficacy, bioequivalence, bioavailability, psychoactive drugs, and excipients. Results: Few
publications compared the bioequivalence and efficacy of brandname and generic psychoactive
drugs. Those that were identified revealed differences in the efficacy and tolerability of brandname and generic psychoactive drugs that had not been noted in the original bioequivalence
studies. Specifically, l study found that plasma levels of phenytoin were 31% lower after a
switch from a brand-name to a generic product. Several controlled studies of carbamazepine
showed a recurrence of convulsions after the shift to a generic formulation. After a sudden
recurrence of seizures when generic valproic acid was substituted for the brand-name product, an
investigation by the US Food and Drug Administration found a difference in bioavailability
between the 2 formulations. Statistically significant differences in pharmacokinetic variables
have been reported in favor of brand-name versus generic diazepam (<F>P < 0.001</F>).
Finally, a case report involving paroxetine mesylate cast doubt on the tolerability and efficacy of
the generic formulation. Conclusion: The essential-similarity requirement should be extended to
include more rigorous analyses of tolerability and efficacy in actual patients as well as in healthy
subjects.
This author conducted research similar to what I am doing now, and his conclusion is similar to
my view that more studies need to be performed. It seems he would be unbiased because he was
looking at multiple sides of the issue like I am. He also does not come to any unfounded
conclusions with his research.
Dunckley, V. (2012, March 26). Brand vs. generic: When it matters (and what to do when it
does). Psychology Today, Retrieved from http://www.psychologytoday.com/blog/mentalwealth/201203/brand-vs-generic-when-it-matters-and-what-do-when-it-does
This is a magazine article that highlights the dangers of generics and how the FDA is ineffective
at evaluating them. It includes information about the antidepressant Wellbutrin and how the
author had heard from many individuals that they suffered adverse reactions to the generic
version, including thoughts of suicide. He contacted the FDA and they told him to fill out an
“adverse event report,” but it seemed to be ineffective in doing anything. He further writes that
sources from a manufacturing plant in India in claim generics are nowhere near the same, and
that manufacturing of generics is generally questionable.
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The author is a writer for Psychology Today so I do not believe he would be biased in one
direction or another. It seems more likely, based on the magazine the article was published in,
that he would want to provide the most accurate information possible since much of his audience
would be psychiatrists or clinical psychologists.
Gaudiano, B., & Miller, I. (2006). Patients' expectancies, the alliance in pharmacotherapy, and
treatment outcomes in bipolar disorder. Journal of Consulting and Clinical Psychology,
74(4), 671-76.
Summary from Abstract: Bipolar disorder is characterized by a chronic and fluctuating course of
illness. Although nonadherence to pharmacotherapy is a frequent problem in the disorder, few
studies have systematically explored psychosocial factors related to treatment discontinuation.
Previous research with depressed patients receiving psychotherapy has suggested that
expectancies for improvement are related to treatment outcomes and that the therapeutic alliance
may partially mediate this relationship. The current study found evidence for a similar
relationship between patients' initial expectancies for improvement, patient and doctor-rated
alliance, and long-term outcomes in bipolar patients treated with pharmacotherapy for up to 28
months following an acute episode. The results highlight the need for the assessment of
expectancies and alliance in bipolar treatment and suggest possible targets for psychosocial
interventions.
This is another source from a peer-reviewed journal, so bias is likely not an issue. This article is
not directly related to the topic of generic or brand-name drugs, but it highlights the importance
of additional factors such as doctor-patient relationship and expectations in treatment outcomes.
Because research entirely related to my topic is limited, this study suggests that the potential
harms of generic medications could be avoided by thoroughly explaining them to the patients.
History of generic drugs. (2013). Retrieved from http://ipharmacylist.com/meds/history-ofgeneric-drugs.html
This internet source tells how the generic drug market came to be, saying that it started with a
generic version of Bayer aspirin in the 1920’s. There is no author listed on the website, but it still
gives a plethora of information on the history of this market. Regulations have varied in the
United States throughout the last 90 years, with the most recent legislation only requiring proof
of bioequivalence of the generic drugs.
Because there is no credited author, I cannot evaluate bias based on their credibility. However,
this is a source for objective historical information, and thus there is likely no bias.
Howland, R. H. (2010). Are generic medications safe and effective?. Journal Of Psychosocial
Nursing And Mental Health Services, 48(3), 13-16. doi:10.3928/02793695-20100204-01
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Summary from Abstract: Because multiple branded, alternative, and generic medications contain
the same active ingredient, controversies sometimes arise regarding generic substitution. For
patients, physicians, and nurses, the critical issue is whether generic medications are safe and
effective. This article addresses the issue with regard to several antidepressant, anticonvulsant,
and antipsychotic medications. There is no consistent evidence that generic substitutes are less
safe or less effective than brand-name equivalents. Uncontrolled reports are subject to many
confounding factors and biases. Relapses temporally associated with medication switches could
be due to the change but are difficult to distinguish from the natural history of the treated
condition. Adverse effects temporally associated with medication switches could also be
attributable to the change, but they might be explained as a type of "nocebo" effect. Expectancy
theory may be used to explain relapses or adverse effects after generic switches. Randomized
controlled blinded studies are necessary to evaluate causality; however, such studies typically
have not supported uncontrolled reports that the safety or effectiveness of brand-name and
generic drugs differ. It is still clinically prudent to monitor a patient whose medication has been
switched.
R.H. Howland seems to be a very credible source, as he has published multiple research articles
on the subject of bioequivalence of brand-name and generic drugs. I do not believe him to be
biased because he must have a great deal of knowledge on the subject at this point.
Margolese, H. C., Wolf, Y., Desmarais, J., & Beauclair, L. (2010). Loss of response after
switching from brand name to generic formulations: Three cases and a discussion of key
clinical considerations when switching. International Clinical Psychopharmacology,
25(3), 180-182. doi:10.1097/YIC.0b013e328337910b
Summary from Abstract: Generic formulations of medications are marketed as therapeutically
equivalent and less expensive than branded ones. Multiple studies and case reports have
described relapses and worsening clinical outcome in patients after a switch from a brand name
to a generic medication. Recent studies have shown that generics do not always lead to the
expected costs savings, reducing the impetus to proceed with compulsory generic switching. We
report on three patients who experienced clinical deterioration after commencing the generic
formulation of their previous brand name psychotropic medication. We discuss key clinical
differences between original and generic formulations of the same medication. The use of bio
equivalence as an indicator of therapeutic and clinical equivalence, the lack of appropriate
studies comparing generic and brand name medications and differences in excipients are some of
the factors that could explain variation in clinical response between generic and brand name
medications. Generic switching should be decided on a case-by-case basis with disclosure of
potential consequences to the patient.
These authors have all been published in similar research to this, and the fact that they specify
they are only looking at case studies somewhat exempts them from bias. Case studies are not
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meant to be generalized, so their conclusions are limited but this research still gives me examples
of instances when switching to generics can be dangerous.
Roman, B. (2009). Patients’ attitudes towards generic substitution of oral atypical antipsychotics:
A questionnaire-based survey in a hypothetical pharmacy setting. CNS Drugs, 23(8), 693701. doi:10.2165/00023210-200923080-00006
Summary from Abstract: Generic atypical antipsychotics in tablet form differ in name,
appearance and packaging from the innovator brand antipsychotics. These differences might
cause anxiety, confusion and misperceptions in some ambulant patients with
psychoses/schizophrenia, especially if the brand atypical antipsychotic is substituted in the
pharmacy without the acknowledgement of the patient and treating psychiatrist. Furthermore,
generic substitution of branded oral atypical antipsychotics in the pharmacy might cause nonadherence and potentially lead to suboptimal treatment outcomes if patients perceive the
medicines to be clinically different. Objective: To determine the attitudes of patients with
psychoses/schizophrenia towards generic substitution of oral atypical antipsychotics in a
pharmacy setting. Methods A total of 106 ambulant patients with psychoses/schizophrenia
currently taking an oral atypical antipsychotic (risperidone [Risperdal®], olanzapine
[Zyprexa®], quetiapine [Seroquel®] or aripiprazole [Abilify®]) were confronted with generic
substitution in a hypothetical pharmacy setting. Two conditions were used: one granting patients
a short explanation about the substitution, and one without explanation. Patients' attitudes
towards the generic substitution were assessed using a combined quantitative and qualitative
design. Results Of the respondents, 73% stated that they would be unlikely to take a generic
antipsychotic if their pharmacist were to substitute it. Providing patients with a short explanation
had a significantly positive effect on their intention to take a generic version; however, overall,
the patients' intention to take the generic antipsychotic lay well below a neutral midpoint.
Conclusion Patients with psychoses/schizophrenia using atypical antipsychotics in tablet form
perceive generic versions of their antipsychotics as being significantly different. This perceived
difference lowers their intention of continuing to take the medication, thus possibly jeopardizing
treatment outcome. Caution with the generic substitution of atypical antipsychotics in the
pharmacy is therefore recommended. Generic substitution should take place only with the
knowledge and agreement of the psychiatrist and the patient.
The study that Roman performed used two conditions, so bias could only be found in the fact
that all of the patients who took part in the study were living in hospitals. This looked at
individuals with one of the more serious mental illnesses, which is an important part of looking
at generic drug substitution as the effects on these individuals could be the most consequential.
Sansone, R., & Sansone, L. (2010). Psychiatric disorders: A global look at facts and figures.
Psychiatry, 7(12), 16-9. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028462/
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Summary from Abstract: According to data from Western countries, psychiatric disorders are
relatively prevalent. For example, in the United States general population, data from the National
Comorbidity Survey Replication study indicate that about one-quarter of individuals experience
a psychiatric disorder in a given year, with lifetime rates at about 50 percent. For both prevalence
designations, anxiety disorders are most common. According to data from the European Study of
the Epidemiology of Mental Disorders, the 12-month and lifetime-prevalence rates for
psychiatric disorders among European general populations are 11.5 and 25.9 percent,
respectively, with mood and anxiety disorders evidencing approximately equal rates. As
expected, in primary care settings, the prevalence of psychiatric disorders in the United States
and Europe is high, with point-prevalence rates varying, but affecting approximately 25 to 30
percent of patients. In primary care settings, the most common psychiatric diagnoses are mood
and anxiety disorders as well as somatoform disorders. While no global summary of cost of care
is available, the high prevalence rates of psychiatric disorders correspond with high expenditures
for mental healthcare, as evidenced by a number of sources. Given these latter findings,
prevention becomes all the more relevant in terms of cost management.
The authors of this study are both psychiatrists and are looking at objective facts and figures, so
there is no bias. These statistics help draw attention to the importance of my research, because
about half of the United States will have a diagnosable psychiatric disorder at some point in their
lives.
Solomont, E. B. (2008, July 16). Insurers pay doctors to push generic drugs. New York Sun.
Retrieved from http://www.nysun.com/business/insurers-pay-doctors-to-push-genericdrugs/81992/
This online newspaper article explains how an insurance company in Rochester, N.Y. was
offering doctors higher compensation for increasing the percentage of generic drugs they
prescribe to their patients. The article includes quotes from doctors and the American Medical
Association about how this kind of deal sets a dangerous precedent for how doctors should be
treating their patients.
The author is a reporter for this online newspaper, and he had sources on both sides of the issue
in this article to reduce bias. For example, Solomont includes sources that claim there should not
be regulations on this kind of practice because people need affordable healthcare; conversely, he
includes sources that claim trying to switch more patients to generics could be dangerous.