Tag Archives: pharmacotherapy

Major Depressive Disorder (MDD) treatment options – Examining the STAR*D Trial


When weighing the effectiveness of Major Depressive Disorder (MDD) treatment options, the most logical place to start is the largest open-label pragmatic trial ever rendered; The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial.  The STAR*D trial concluded that there were no statistically significant differences in short term remission or response rates between tested treatment options, including both CBT and pharmacological remedies, but that some treatment options had advantages over others in terms of side effects and/or mean time to remission.  (Sinyor, Schaffer, & Levitt, 2010)

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There are many different flavors of CBTs intended to treat mood disorders.  Those flavors include those predominantly focused on learning theory or behavioral activation (BA), predominantly cognitive models such as Cognitive Therapy (CT/CBT), and models incorporating additional elements such as Cognitive Behavioral Analysis System Psychotherapy (CBASP) and Mindfulness-Based Cognitive Behavioral Therapy (MCBT).  (Meyer & Scott, 2008, p. 685)  CBT, when practiced by inexperienced STAR*D clinicians, was at least equally effective in short term follow-ups when compared with pharmacological remedies.  CBT was also associated with significantly fewer side effects.  Those facts alone should serve as reasonable justification in recommending CBT over all other treatment methods.

CBT was associated with longer times to remission when compared with pharmacological remedies, when they were effective, so if speed of improvement is of critical importance the client could potentially benefit the pharmacological treatment option.  Despite the apparent speed with which the pharmacological agents worked, choosing which drug is no easy task.  STAR*D found no clear medication “winner” for patients whose depression does not remit after one or more aggressive medication trials.  (Gaynes, Warden, Trivedi, & Wisniewski, 2009, p. 1443)  Matter of fact, every drug and combination of drugs showed the same effect as every other drug and drug combination.  (Leventhal & Antonuccio, 2009)  Some studies suggest that use of multiple antidepressant medications may double the likelihood of remission compared with use of a single medication.  (Blier, Ward, Tremblay, & Laberge, 2010)  Guess who funded that study?

There is increasing evidence that the biological explanation and pharmacological treatment of depressions is a failure.  STAR*D provides compelling evidence to that the placebo effect is the prime explanation for favorable outcomes that occur with antidepressants.  Of the patients that were found to respond positively to pharmacotherapy on the short term, the STAR*D study found that at the end of a year’s time almost all of the patients (97%) had either relapsed or dropped out.  (Leventhal & Antonuccio, 2009)  Even if we continue to leverage the pharmacological remedies, the long-range outcomes of clients with MDD are better when CBT is included, regardless of whether CBT is concurrent with or follows pharmacotherapy.  (Friedman, Wright, Jarrett, & Thase, 2006, p. 327)  The beneficial effects of CBT persist several years into post treatment and are strongly associated with preventing relapse (Kuyken, Dalgleish, & Holden, 2007), especially among individuals discontinuing medication use.  (Friedman, 2004)

As controversial as they are, “brain stimulation therapies” like electroconvulsive treatment (ECT) are effective in days, not weeks, and most have a higher response rate than any treatment tested in the STAR*D trial.  (Insel & Wang, 2009)  While ECT is still the gold standard in brain stimulation therapies, clinicians now have a growing list of FDA approved brain stimulation interventions. “These interventions include new modifications of ECT, vagus nerve stimulation, transcranial magnetic stimulation (TMS), magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, implanted cortical stimulation, and others on the horizon.”  (Lisanby & Novakovic, 2009, p. 734)  Studies that utilized brain stimulation therapies to treat depression revealed significant increases in the release of norepinephrine as well as increased serotonergic activity, both of which are purported to have antidepressant effects.  (Weaver, 2009)  However, ECT is use is “limited by its invasive nature, which includes the requirement of general anesthesia and the risk of retrograde amnesia, which may be irreversible in some patients.”  (Rot, Mathew, & Charney, 2009, p. 311)  As a result, brain stimulation therapies are usually reserved for cases where depression is resistant to conventional treatments.  In addition, use of brain stimulation therapy is entirely dependent on the prescribing clinician believing in a tenuous underlying premise that norepinephrine plays a key role in depression onset and recurrence.

It would suffice to say that I favor the CBT methodology of treatment for unipolar depression, in most, if not all cases.  Personally, I would endeavor to enhance the CBT experience by utilizing cutting edge technological alternatives to traditional CBT… like virtual reality, or VR, simulations.  VR simulations are computer generated environments constructed to elicit an appropriate emotional response from clients… responses we as therapists can use in therapy.  (David, 2010)  Coupling responses that rival in vivo responses with well trained and knowledgeable CBT methods, we could usher in a new alternative to the placebo effect that passes for pharmacological intervention today.  The failure of antidepressants to provide lasting benefit, and the underlying truth that 100 years of research has failed to identify an underlying physical cause for mental disorders (including depression) leads me to believe that a “biopsychosocial model may be more useful than a disease model for conceptualizing and treating depression.”  (Leventhal & Antonuccio, 2009, p. 199)

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References

Blier, P., Ward, H. E., Tremblay, P., & Laberge, L. (2010, Mar). Combination of antidepressant medications from treatment initiation for major depressive disorder: A double-blind randomized study. The American Journal of Psychiatry, 167(3), 281-288. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1976013231&sid=18&Fmt=4&clientId=4683&RQT=309&VName=PQD

David, D. (2010, Mar). Cutting edge deveopments in psychology: Virtual reality applications. Interview with two leading experts. Journal of Cognitive and Behavioral Psychotherapies, 10(1), 115-126. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=2010171911&sid=2&Fmt=3&clientId=4683&RQT=309&VName=PQD

Friedman, E. S., Wright, J. H., Jarrett, R. B., & Thase, M. E. (2006, May). Combining cognitive therapy and medication for mood disorders. Psychiatric Annals, 36(5), 320-329. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1069483751&sid=4&Fmt=3&clientId=4683&RQT=309&VName=PQD

Friedman, M. A. (2004, Spring). Combined psychotherapy and pharmacotherapy for the treatment of major depressive disorder. Clinical Psychology: Science and Practice, 11(1), 47-68. Retrieved from http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?index=40&did=526558591&SrchMode=1&sid=5&Fmt=10&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1272666830&clientId=4683

Gaynes, B. N., Warden, D., Trivedi, M. H., & Wisniewski, S. R. (2009, Nov). What did STAR*D teach us? Results from a large-scale, practical, clinical trial for patients with depression. Psychiatric Services, 60(11), 1439-1445. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1921563151&sid=2&Fmt=3&clientId=4683&RQT=309&VName=PQD

Insel, T. R., & Wang, P. S. (2009, Nov). The STAR*D trial: Revealing the need for better treatments. Psychiatric Services, 60(11), 1466-1467. Retrieved from http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?index=28&did=1921563061&SrchMode=1&sid=6&Fmt=6&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1272667182&clientId=4683

Kuyken, W., Dalgleish, T., & Holden, E. R. (2007, Jan). Advances in cognitive-behavioural therapy for unipolar depression. Canadian Journal of Psychiatry, 52(1), 5-14. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1203220561&sid=5&Fmt=3&clientId=4683&RQT=309&VName=PQD

Leventhal, A. M., & Antonuccio, D. O. (2009). On chemical imbalances, antidepressants, and the diagnosis of depression. Ethical Human Psychology and Psychiatry, 11(3), 199-214. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1923231211&sid=19&Fmt=3&clientId=4683&RQT=309&VName=PQD

Lisanby, S. H., & Novakovic, V. (2009, Jun). Brain stimulation therapies for clinicians. The American Journal of Psychiatry, 166(6), 734-736. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1738370431&sid=14&Fmt=3&clientId=4683&RQT=309&VName=PQD

Meyer, T. D., & Scott, J. (2008, Nov). Cognitive behavioural therapy for mood disorders. Behavioural and Cognitive Psychotherapy, 36(6), 685-693. doi: 10.1017/S1352465808004761

Rot, M. A., Mathew, S. J., & Charney, D. S. (2009, Feb 3). Neurobiological mechanisms in major depressive disorder. Canadian Medical Association. Journal, 180(3), 305-313. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1634710771&sid=14&Fmt=3&clientId=4683&RQT=309&VName=PQD

Sinyor, M., Schaffer, A., & Levitt, A. (2010, Mar). The sequenced treatment alternatives to relieve depression (STAR*D) trial: A review. Canadian Journal of Psychiatry, 55(3), 126-136. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=2016794701&sid=2&Fmt=3&clientId=4683&RQT=309&VName=PQD

Weaver, D. F. (2009, Summer). Self-induced “therapeutic seizures” for the treatment of depression. The Journal of Neuropsychiatry and Clinical Neurosciences, 21(3), 355-357. Retrieved from http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?index=71&did=1868802651&SrchMode=1&sid=14&Fmt=3&VInst=PROD&VType=PQD&RQT=309&VName=PQD&TS=1272668233&clientId=4683

Separation Anxiety Disorder (SAD)


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In order to qualify for a DSM-IV-TR (2000) diagnosis of Separation Anxiety Disorder (SAD; 309.21), a client must present with the following essential features:

A)    Developmentally inappropriate and excessive anxiety concerning separation from home or from those to whom the individual is attacked, as evidenced by three (or more) of the following:

  1. Recurrent excessive distress when separation from home or major attachment figures occurs or is anticipated
  2. Persistent and excessive worry about losing, or about possible harm befalling, major attachment figures
  3. Persistent and excessive worry that an untoward event will lead to separation from a major attachment figure (e.g., getting lost or being kidnapped)
  4. Persistent reluctance or refusal to go to school or elsewhere because of fear of separation
  5. Persistently and excessively fearful or reluctant to be along or without major attachment figures at home or without significant adults in other settings
  6. Persistent reluctance or refusal to go to sleep without being near a major attachment figure or to sleep away from home
  7. Repeated nightmares involving themes of separation
  8. Repeated complaints of physical symptoms (such as headaches, stomachaches, nausea, or vomiting) when separation from major attachment figures occurs or is anticipated.

B)    The disturbance must last for a period of at least 4 weeks.

C)    The disturbance must begin before age 18.

D)    The disturbance causes clinically significant distress or impairment in social, academic (occupational), or other important areas of functioning.

E)     The disturbance does not occur exclusively during the course of a Pervasive Development Disorder (PDD), Schizophrenia, or other Psychotic Disorder and, in adolescents and adults, is not better accounted for by Panic Disorder with Agoraphobia.  (American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2000, p. 125)

Separation Anxiety Disorder (SAD) is not uncommon; prevalence estimates average about 4% in children and young adolescents.  SAD decreases in prevalence as kids get older.  (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000, p. 123)  Some researchers argue that SAD is actually an early manifestation of panic disorder, rather than just a risk factor or precursor.  (Jurbergs & Ledley, 2005)

Treatment of SAD often involves a multimodal approach that may include psycho-education of the patient and family, school consultation and intervention, pediatrician consultation and pharmacotherapy, and cognitive-behavior therapy (CBT).  Research has repeatedly demonstrated the efficacy of CBT for children with SAD, supporting it as the best-proven treatment.  (Jurbergs & Ledley, 2005)  CBT has become a respected and empirically established model of psychotherapy in adults.  The fundamental principles of CBT can be applied to children with developmental modifications.  David Dia’s (2001) case study of a six year old boy named “Colt” serves as a great example.  Utilizing family education, progressively more difficult stress scenarios, and a token/exchange system; Colt’s belief was challenged and modified.  (Dia, 2001)

Although the cognitive technique of guided discovery and education proved fruitful in Colt’s case, I would underscore the importance of modifying CBT methods that were traditionally designed for adult patients.  Grover and associates (2006) provide the following examples of modification:

Relaxation and breathing techniques can be adapted for the younger child by using balloon (e.g., breath in and make your tummy fill up like a balloon) and robot/rag doll (e.g., tense your muscles like a robot, relax like a rag doll) metaphors. Depending on the cognitive level of the child, cognitive restructuring techniques may be simplified to teaching the child self-statements like, “Everything will be OK,” or, “I can handle my worries by myself.” One 9-year-old boy with SAD liked to use the coping statement, “Mom has always come back for me before.”  (Grover, Hughes, Bergman, & Kingery, 2006)

Pharmacotherapy should be used in conjunction with CBT only when the child’s symptoms have not responded to CBT interventions alone.  Selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and benzodiazepines have all been used to treat a number of anxiety disorders in children, including SAD, but no medications have specific indications for SAD.  (Jurbergs & Ledley, 2005)

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References

American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.). Washington, DC: Author.

Dia, D. A. (2001, May). Cognitive-behavioral therapy with a six-year-old boy with separation anxiety disorder: A case study. Health & Social Work, 26(2), 125-129. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=73283346&sid=4&Fmt=3&clientId=4683&RQT=309&VName=PQD

Grover, R. L., Hughes, A. A., Bergman, R. L., & Kingery, J. N. (2006, Fall). Treatment modifications based on childhood anxiety diagnosis: Demonstrating the flexibility in manualized treatment. Journal of Cognitive Psychotherapy, 20(3), 275-287. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=1126879061&sid=6&Fmt=3&clientId=4683&RQT=309&VName=PQD

Jurbergs, N., & Ledley, D. R. (2005, Sep). Separation anxiety disorder. Psychiatric Annals, 35(9), 728-736. Retrieved from http://ezproxy.bellevue.edu:80/login?url=http://proquest.umi.com.ezproxy.bellevue.edu/pqdweb?did=905192971&sid=6&Fmt=4&clientId=4683&RQT=309&VName=PQD