Transcript 6bulimiatreament

Assessment Therapy
The treatment I will be assessing is that of Selective
Serotonin Re-uptake Inhibitors (SSRI’s) in the
treatment of Bulimia
Background
• Bulimia affects anywhere between
• 1.7%-2.5% of women
• 6% of adolescent girls
• 5% of college women
(Alexander)
History Of SSRI’s
• SSRI’s were introduced in 1987.
• The first was Fluoxetine (Prozac:Eli Lilly & Company) FDA approved
1987
• Sertraline (Zoloft; Pfizer, Inc) FDA approved 1991
• Paroxetine (Paxil; GlaxoSmithKline) FDA approved 1992
• Citalopram (Celexa; Forest Pharmaceuticals) FDA approved 2000
• Escitalopram (Lexapro; Forest Pharmaceuticals) FDA approved
2002
• alaproclate
• Etoperidone
• Fluvoxamine
• Zimelidine
History of SSRI’s
• SSRI’s are serotonin boosters.
• They act to restore chemical balance in the brain.
• SSRI’s act on the neurotransmitter serotonin. It blocks
the re-uptake of serotonin at the synaptic cleft, thus
making more serotonin available at the post synaptic
nerve.
• Scientists and doctors are not quite sure how serotonin
works but they are aware of its effects in the control :
• Mood
• Sleep
• Body temperature
• Appetite
Serotonin
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Serotonin:
“A compound, also known as 5-hydroxytryptamine (5-HT), derived from
tryptophan, an amino acid. It is widely distributed in the animal and
vegetable kingdoms. In mammals it is found in gastrointestinal
enterochromaffin cells, in blood platelets, and in brain and nerve tissue.
Serotonin is a local vasoconstrictor, plays a role in brain and nerve function
and in regulation of gastric secretion and intestinal peristalsis, and has
pharmacologic properties. Serotonin is concentrated in certain areas of the
brain; the hypothalamus and midbrain contain large amounts, while the
cortex and cerebellum contain low concentrations. When a serotonincontaining nerve fires, serotonin is released and can bind to any one of a
series of at least 14 distinct downstream serotonin receptors (5-HT
receptors). SSRIs, act by increasing the amount of active serotonin in nerve
synapses in particular brain regions. Conversely, various conditions that
lower serotonin levels are associated with depression, suggesting that
normal to slightly elevated serotonin levels tend to elevate mood and
prevent depression”.(McGraw-Hill Encyclopedia of Science and Technology,
2005)
Serotonin and Bulimia
• This relates to the neurobiology of Bulimia
because bulimics have reduced serotonin
• The most common SSRI’s used in the
treatment of bulimia are;
• Fluoxetine
• Fluvoxamine
• Paroxetine
• Most of the bulimia research focuses on
Fluoxetine
History Of Fluoxetine (Prozac)
It was invented at EliLilly by a team of scientists headed by
• Dr. Ray W. Fuller
• Drs. Bryan B. Molloy
• David T. Wong
• They were awarded the Pharmaceutical Discoverers Award from the
NARSAD (National Alliance for Research on Schizophrenia and
Depression)
• Prozac originated from Diphenhydramine, which inhibits the reuptake of serotonin, discoved in 1960. However, Diphenhydramine
had many side effects. Hence Dr. Fuller and his team wanted to
invent a drug that produced the same effects as Diphenhydramine
but with fewer side effects.
• Prozac was then invented, the first of the SSRI’s. The drug became
very popular due to the extensive marketing by Lilly.
History of Fluoxetine
• In 2001 Barr Laboratories disputed Lilly’s patent
to Prozac, and they were successful. Today
many companies produce Fluoxetine.
Fluoxetine is approved for use in;
• Obsessive Compulsive Disorder (OCD)
• Depression
• Bulimia
• Premenstrual Dysphonic Disorder
• Panic Disorder
Side Effects
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Akathisia - Motor restlessness, an inability to sit still or lie quietly.
Rage
Restlessness & Insomnia
Weight Loss & Weight Gain
Trembling
Weakness
Skin Rash
Anorgasmia - Failure to achieve orgasm (climax) during sexual
intercourse.
Itching
Decrease In Sexual Drive
Hyponathraemia - A deficiency of sodium in the blood.
Suicidal Thoughts
Formulations
• Sold in capsules of 10, 15, 20, 40, 60 or 90mg.
• Prozac weekly-90mg pill with a 7 day slow release
• The typical dosage of a bulimic is 60mg/day as compared to that of
20mg for people with depression and OCD
• Levels should not exceed 80mg/day
• Overdose: 16 confirmed, the amounts varied from 80mg-200mg in
persons ranging from 13-51 years of age. No deaths occurred.
They were all treated with charcoal. Most people who overdose on
any drug get treated with charcoal.
• 2 deaths occurred because the drug was mixed with alcohol and
other drugs.
Pharmokinetics
• Fluoxetine is absorbed between 1.5-12hrs
depending on the oral dose
• It takes 4 to 5 weeks of continuous uses to
achieve steady blood plasma states
• Bulimics achieve the best results after 16 weeks
of use
• After discontinuing the drug it may take between
1 and 2 months for the active drug substances to
disappear from the body
Research
• Psychopharmacotherapy of anorexia nervosa, bulimia nervosa
and binge-eating disorder. (Kruger, Sidney, Kennedy) Journal of
Psychiatry & Neuroscience, 2000.
• This research suggests that fluoxetine has been shown to interrupt
the binge-eating/purging cycle, even in the absence of depressive
symptoms. Fluoxetine is the most rigorously studied SSRI for the
treatment of bulimia nervosa.
• Fluoxetine treatment must be followed for a least 6 months to
reduce the chances of relapse.
• This articles suggests that patients with bulimia may suffer from a
serotonin (5-HT) deficit. 5-HT receptors are responsible for our
response to stimuli i.e. food. 5-HT also allows us to regulate our
affective states and moods, and may play a major role in our
impulses.
Research
• This 5-HT deficiency is said to be the
driving force behind the dieting, bingeeating and purging associated with the
disorder. And it is the SSRI’s that block
the re-uptake of serotonin making more
available at the 5-HT receptor sites, hence
“normalizing” the serotonin levels in the
brain accounting for the anti-bulimic
effects of fluoxetine.
Research
• Ghrelin concentrations and cardiac vagal tone are decreased
after pharmacologic and cognitive-behavioral treatment in
patients with bulimia nervosa. (Tanaka, Nakahara, Muranaga,
Kojima, Yasuhara, Ueno, Nakazato, Inui) Hormones and Behavior,
2006.
• The purpose of this study was to show if the SSRI paroxetine
combined with cognitive behavioral treatment alleviated the bulimic
symptoms of increased Ghrelin, decreased leptin, decreased vagal
tone.
• Ghrelin simulates growth hormone secretion. It increases food
intake, enhances appetite and antagonizes leptin action. These all
have an effect on eating behavior and energy metabolism via the
CNS and the vagal system.
Research
This study has shown that bulimics have
• Increased Ghrelin
• Decreased leptin
• Decreased vagal tone
Participants:
• 24 female bulimic patients 19-32 years of age who met the DSM criteria for
the disorder, were free of any drugs for 3 months. They had to have bingeeating and vomiting at least 2 times/week for 3 months
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25 matched female volunteers who had no history of eating disorders or
mental disorders, with normal blood tests.
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For 16 weeks the bulimics took 20mg of paroxetine daily before bed, and 50
min of CBT. Blood work was done before the 16 weeks and after the
16weeks of treatment. A POMS depression scale was conducted prior to
treatment and after treatment.
Research
• The finding of this study suggest the SSRI
paroxtine & CBT;
• Decrease fasting Gherlin levels
• Decreased resting cardiac tone
• Decreased binge-eating
• Decreased there scores on the depression scale
(POMS)
• The finding of this study suggest that habitual
abnormal eating behavior might be related to the
abnormal function of gastrointestinal hormones
via the vagal system.
Research
Strengths of the study:
• These finding are important to the future treatments of bulimia
because it has provided doctors with a measure of bulimia via blood
work (measuring Ghrelin, lipin and vagal tone). This provides
doctors with a base line to asses if a pharmacologic treatment is
effective.
Weakness of the study.
• The control group should have been bulimics who did not receive
treatment. They should have looked at both treatment options
independently. Here we are not exactly sure which treatment is
actually causing the person to improve. The improvements can be
attested to the CBT or the paroxtine or a combination of the two, it
isn’t very clear. A lot of the research in this field uses a combination
of treatments so it is hard to distinguish which treatment is improving
the overall condition of the patient.
Brain Areas
affected/Neurobiology:
• Fluvoxamine, a selective serotonin reuptake inhibitor appetitesuppressing effects in mice 5-HT1B receptors. (Nonogaki,
Nozue, Takahashi, Yamashita, Hiraoka, Kumano, Kuboki, Oka)
International Journal of Neuropsychopharmacology, 2006.
• This study demonstrated that SSRI’s selective at the 5-HT2c
receptor antagonist enhances the increase of extra cellular 5-HT
levels induced by SSRI citapran in the hippocampus.
• That fluoxetine increases the extra cellular 5-HT levels in the
prefrontal cortex and the hippocampus.
• That fluvoxamine increased extra cellular 5-HT concentrations, by
inactivating the 5-HT2c receptor, this increases the 5-HT1b receptor
gene expression and more serotonin is available at the synaptic cleft
because it blocks the re-uptake of serotonin.
Evaluation:
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Advantages:
SSRI’s have relatively few side effects when compared to other antidepressants
SSRI’s are cost effective
SSRI’s are readily available
SSRI’s have been prove to be anti-bulimic
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Disadvantages:
SSRI’s have drug interactions with other medications and alcohol.
SSRI’s have been studied in conjunction with other therapies, hence we are not truly
certain which treatment is benefiting the patient
There are many 5-HT receptor types, hence we aren’t certain which sites are affected
by bulimia and which drugs will target a specified 5-HT receptor.
We don’t know much about the mechanisms of action of these drugs, in many cases
we know that they just work, but we don’t know how they specifically work
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Conclusions:
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The use of SSRI seems to provide promise in the treatment of bulimia.
More studies need to be done assessing the specific effects of drug
treatment on this condition, rather then using a combination of treatments.
It seems as though there is limited research on SSRI’s, most of the
research available focuses on a few of the SSRI’s, perhaps because they
are fairly new in there evolution. It is also important that scientist
understand the underlying causes of bulimia. We are not really sure if the
behaviors of the disorder account for the brain abnormalities present in
these patients or if these patients were born with these brain abnormalities
which caused them to develop bulimia. How can we effectively treat a
disorder if we aren’t exactly sure of its causes? It is also very complicated
to asses the possible causes of the disorder because we do not know who
will become bulimic; hence we cannot assess them prior to the onset of
illness, a major draw back. Evidence for the anti-bulimic affects of SSRI’s
have shown promise in the treatment of bulimia however more research
needs to be conducted because we are still in the infancy of using
pharmacological treatments for this disorder.