Are Antidepressants Really Effective

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Are Antidepressants Really Effective?

• Kim The Optimist Oswald
• Adam The Pessimist Perkins
• PY718 6/17/08

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Summary

• Anti-depressants arent a panacea, by any means,
  but they have their place in the treatment of
  psych disorders.

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Antidepressants

• Tricyclic antidepressants
• Amitriptyline (Elavil)
• Monoamine oxidase inhibitors (MAOIs)
• Phenelzine (Nardil)
• Tetracyclic antidepressants
• Mitrazapine (Remeron)
• SNRI
• Duloxetine (Cymbalta)
• SSRI
• Fluoxetine (Prozac)
• NDRI
• Bupropion (Wellbutrin)
• Combined reuptake inhibitors and receptor
  blockers
• Desyrel (Trazodone)

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Reviewed Articles

• Kirsch, I., Moore, T. J., Scoboria, A.,
  Nicholls, S. S. (2002). The emperors new drugs
  An analysis of medication data submitted to the
  U.S. Food and Drug Administration. Prevention
  Treatment, 5(1).
• Antonuccio, D. O., Burns, D. D., Danton, W. G.
  (2002). Antidepressants a triumph of marketing
  over science. Prevention Treatment, 5(1).

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Kirsch et al., (2002)

• Meta-analysis of clinical trials of
  antidepressants approved by the FDA between 1987
  and 1999.
• Restricted to the 6 most widely prescribed SSRIs
• Prozac
• Paxil
• Zoloft
• Effexor
• Serzone
• Celexa
• 47 trails included
• All but one utilized Hamilton Depression Scale
  (HAM-D)

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Results of Kirsch et al., (2002)

• (a) 82 of the response to medication was
  duplicated in placebo control groups
• (k) 18 of the sample taking antidepressants
  improved.
• (k) Improvement was significant regardless of
  using observed cases (OC) or last observation
  carried forward (LOCF) data

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Results of Kirsch et al., (2002)

• (k) The mean difference between drug and placebo
  affect for 3 of the drugs 1.80 pts on the
  Ham-D. Which is statistically significant.
• (a) Although statistically significant,
  difference may not be subjectively noticeable by
  the participants

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Results of Kirsch et al., (2002)

• (a) Improvement was not associated with dose
  amount
• (k) Some people who didnt respond to the drug,
  may have had a sub-clinical dose (i.e. the does
  might not have been high enough for them)

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Conclusion of Kirsch et al., (2002)

• Antidepressants are effective, but only for a
  small portion of the population

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Antonuccio et al., (2002)

• Commentary on Kirsch et al., (2002)
• Conclusion
• Antidepressants arent as effective as Kirsch
  and colleagues indicated

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Review of Antonuccio et al., (2002)

• (a) Kirsch and colleagues overestimates the
  effect of antidepressant effect by penalizing the
  placebo conditions and/or boosting the drug
  condition.

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Review of Antonuccio et al., (2002)

• Due to design problems
• (a) Washout procedure elimination of
  antidepressant non-responders and placebo
  responders.
• (a) Impossible for studies to be completely
  double blind because clinicians can detect side
  effects of drugs. Therefore, clinician ratings
  maybe biased
• (a) Subjects using sedative medication were not
  excluded
• (a) Conflict of interest in pharmaceutical
  industry funded clinical trials

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Review of Antonuccio et al., (2002)

• (a) Lack of evidence for effectiveness
• Only about 15 of patients in a typical
  outpatient primary care clinic would qualify to
  participate in most antidepressant trials
• (k) The other 85 may respond better to
  antidepressants than those that meet the criteria
  for the clinical trials
• (a) Of the 15 that qualify, only a portion of
  those will actually enroll in the study. Those
  who are willing to participate in a drug study
  may bias the results by possibly inflating the
  effects of the drugs
• (k) Those willing to participate may also inflate
  the placebo effect and thereby decrease the
  difference between the drug and placebo group

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Reviewed Book Material

• Roth Fonagy (2005) What Works for Whom
• Barlow (2001) Clinical Handbook of Psychological
  Disorders, 3rd Edition

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Argument FOR Antidepressants
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All options arent available to all patients all
the time

• Consider people who
• Live in rural areas without access to a therapist
• Have limited or no mental health insurance
• Arent aware of psychotherapeutic options
• Arent comfortable seeking out psychotherapy
• For these individuals, antidepressants might be
  the best option.

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M.D.s The Gateway to Therapy?

• Ever met someone who was scared to go to a
  therapist but was totally fine with going to an
  M.D.s office full of pills and needles?!?
• There are people who will see an M.D. for psych
  symptoms before seeing a psychologist.
• While M.D.s can sometimes be antidepressant
  pushers, this might not be all bad
• The antidepressants might actually help the
  person
• Whether meds help the person or not, they might
  be a motivator for the person to see a
  psychologist for added help

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Additional factors to consider

• Proper implementation of antidepressants is
  essential if we expect them to be useful.
  However, its often the case that
• Patients arent receiving adequate dosages
• Was this monitored well in the aforementioned
  studies?
• Patients arent always compliant with their meds
• Maybe since placebos have less side effects,
  patients were more compliant (thus enhancing the
  placebo effect), while those taking
  antidepressants were less compliant (thus missing
  out on drug effect the placebo effect)
• Antidepressants are not one size fits all
• Each of the clinical trials examined used a
  particular antidepressant. However, often
  patients respond to 1 drug better than another.
• Also, it has been suggested that there are some
  illnesses (even some types of depression e.g.
  melancholia) than respond well to antidepressants
  but not to psychotherapy (Roth Fonagy, 2004).

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Antidepressants are not just for depression

• Antidepressants have been shown to be effective
  for other disorders as well
• Bulimia nerovsa
• Psychogenic pain/Somatoform disorder
• Panic disorder
• Smoking cessation
• Irritable Bowel Syndrome
• Premenstrual Dysphoric disorder
• Borderline Personality disorder
• And many others

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Argument AGAINST Antidepressants
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Negative aspects of medication

• Side effects
• Sexual dysfunction
• Agitation
• Sleep disruption
• Gastrointestinal problems
• Agitation
• Weight gain
• Increased suicidal ideation in adolescents
• Drowsiness
• Risk
• Liver failure (e.g. Serzone discontinued in
  2004)
• Death
• Negative interactions
• Other medication (e.g. combining an SSRI or SNRI
  with "triptan" medications for migraine headache
  may lead to Serotonin Syndrome)
• Food or beverage products (e.g. grapefruit)
• Medical conditions (e.g. low blood pressure)
• Alcohol
• Illicit drugs

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Impact of Side Effects on Mental Health

• Increased depressive symptoms due to
• Side effects are added stressors
• Side effects can decrease pro-social behaviors

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Antidepressants alone (without psychotherapy)

• Short term treatment psychotherapy
• Long term treatment psychotherapy or a
  combination of psychotherapy and antidepressants
• Antidepressants alone (without psychotherapy)
  only relieve symptoms but do not treat (or cure)
  depression or anxiousness
• Psychotherapy is generally more effective than
  antidepressants in treating most psychological
  disorders
• When antidepressants are used, they must be used
  in combination with psychotherapy
• More patients receive medications than
  psychotherapy because primary care physicians are
  the first line of treatment

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Antidepressants with Psychotherapy

• Antidepressants for some patients interfere with
  the effectiveness of psychotherapy
• Decreased depressive symptoms (or anxiety)
  reduces the opportunity for patients to confront
  their thoughts, feeling, or behaviors that evoke
  depressive states (or fear/anxiety).
• Lack of coping behaviors makes people susceptible
  for relapse of depression
• May increase reliance on medication and/or
  increase avoidance of confronting problems.
• medications may block physical symptoms of
  anxiety and panic, which are required for
  interoceptive exposure, and/or may block the
  capacity to experience fear, according to
  emotional processing theory, is necessary
  initially in order to achieve final fear
  reduction.
• Medication may reduce the motivation to engage in
  psychotherapy.

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Question Posed

• (a) Does the small effect of antidepressants over
  placebo-effect justify the risks and side effects
  associated with antidepressants?
• (k) Is there anyone who thinks that
  antidepressants have no merit, whatsoever?