CMF Protocol: Prozac

The uncomfortable part of the Changing Minds Foundation protocol is the use of Prozac. Let's address these fears one at a time so you can make the most informed decision possible. Your child is different from every other child so you really need to weigh the pros and cons depending on your particular situation. I discuss my struggles with my decision to use Prozac for Jett in several posts. In this post, however, I try to just give you the studies and some notes for the big picture on Prozac as well as details on Jett's use of it and then how he is now that he is off of it. I wish we did not have to make these tough decisions, but it is part of our job as caregivers for our loved one.

Why do some use Prozac for T21?

Early Pharmacotherapy restores Neurogenesis and Cognitive Performance in the Ts65Dn Mouse Model for Down Syndrome

Conclusions

...The current study shows that it is possible to increase cell proliferation in numerous regions of the postnatal brain in a mouse model for DS [they gave a mouse DS]. We have used fluoxetine [generic version of Prozac] to stimulate neurogenesis [the birth of neurons], because it is an antidepressant widely used by adults and prescribed in children and adolescents (Boylan et al., 2007) and it has no patent aversive effects on somatic development (Bairy et al., 2007; Einarson et al., 2009). Treatment during the early postnatal period restored neurogenesis and led to the restoration of the total number of neurons in the dentate gyrus. This effect was accompanied by the full recovery of a cognitive task. The transfer of these data to the human condition would imply that a simple pharmacological treatment during the earliest phases of development might be exploited to improve neurogenesis and, possibly, mental retardation in infants with DS.

Full article here:
http://www.jneurosci.org/content/30/26/8769.long

Great article about how they discovered that Prozac helps with neurogenesis:
http://seedmagazine.com/content/article/the_reinvention_of_the_self/

Excerpt:

In December 2000, Duman’s lab published a paper in the Journal of Neuroscience demonstrating that antidepressants increased neurogenesis in the adult rat brain. In fact, the two most effective treatments they looked at—electroconvulsive therapy and fluoxetine, the chemical name for Prozac—increased neurogenesis in the hippocampus by 75% and 50%, respectively. Subsequent studies did this by increasing the exact same molecules, especially trophic factors, that are suppressed by stress.
Duman was surprised by his own data. Fluoxetine, after all, had been invented by accident. (It was originally studied as an antihistamine.) “The idea that Prozac triggers all these different trophic factors that ultimately lead to increased neurogenesis is just totally serendipitous,” Duman says. “Pure luck.”

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Disinhibition Plus Instruction Improve Brain Plasticity

Excerpt:

They found that giving the mice fluoxetine allowed the neurons to bypass the retraction phase and go right to the constructive phase. But this constructive remodeling had to occur at the same time as visual stimulation — an instructive clue — from the functioning eye.
“We think this finding could have clinical relevance,” Nedivi said. For example, during stroke rehabilitation, providing instructive activities with fluoxetine might accelerate a brain region’s adoption of a function previously performed by a damaged region.

Full article:
http://www.vadvert.co.uk/health/11835-disinhibition-plus-instruction-improve-brain-plasticity.html
Prozac also treat vision issues in DS. See this post: Prozac Cures Lazy Eye!

When I took Jett off Prozac

On Prozac, I didn't see a sudden difference in Jett although his crossing eyes had slowly cleared up. But, once I took Jett off Prozac for 2 weeks, I saw the major areas that Prozac was helping him.
Off Prozac he was experiencing:
1) Constipation. Does not go at all... I just wait 7 days and make him go... (He went one small drop last night and was in terrible pain.)
2) His eyes are crossing so much that he turns his head all over the place to try to see better.
3) I can't leave him to play independently anymore because he goes and finds a sock or some string to wave in front of his face and goes, "Eeeeeeeeeeeeee," until I redirect him. This may be because of the constipation?
4) I'm the only one he wants. No one else can hold him except sometimes my husband. So I'm back to "wearing him" in a wrap to get anything done & prevent stimming. (Have you ever tried to shape dough into hot dog buns while holding a baby?) But, while holding him, he attempts to stim with the strings on my pants and the straps on my shirt.

On P, he would have fine bowel movements for 2-3 weeks out of the month. His eyes rarely crossed. The stimming was almost completely gone! I didn't really have to worry about it anymore. He'd just play happily and occupy himself.

Update on taking Jett off Prozac 

I got so freaked about Jett's negative reaction to being off Prozac, that I put him back on for a while until I could figure out what to do. So when I took him off again, I added in some tryptophan to help ease the transition and help him produce his own serotonin again and I lowered the dose slowly rather than cold turkey. This worked very well.
I didn't like the fact that Prozac was masking, rather than curing Jett's eye issues and wanted to address them directly. I couldn't do this if I couldn't see the problem. The same with the stimming issues. Without Prozac, I've been able to use vision therapy and address the sensory issues that was causing the stimming. Now his eyes only misalign when he is very tired or looking at something very close up. The developmental vision therapist is very pleased with Jett's eye improvement. As for the stimming, that took some time and effort as well. Now he, again, only stims when he is tired. It makes me immediately realize that I need to put him to down for a nap or for the night. Concerning the constipation, increasing his vitamin C intake and properly addressing his thyroid has eventually eliminated this problem as well.
There were also many supplements that Prozac interfered with that I wanted to try. So that was another motivation to take Jett off.

Positive effects I've seen with Jett OFF Prozac

Once I got past the first bout of the negative effects of taking him off, I was able to realize how much better off he was NOT on Prozac. I realized that his speech actually stalled the entire time and even regressed a bit on it. Once he was off, his speech just skyrocketed again. Fortunately, before Prozac, his speech was stellar so even with the stalling, he wasn't too far behind and quickly progressed. So, all in all, giving Prozac was something that I needed to try, but now I really feel that he's better off without it. Not knowing the true and long term side effects just didn't sit well with me and kept me up at night.

Possible drug interactions
 
L-tryptophan (found in Nutrivene DS formula & night time formula) 
5-HTPL-dopa
anorexiants
anticonvulsants
antidepressants
anxiolytics
calcium channel blockers
cyproheptadine
lithium salts
drugs of abuse

Reports have suggested that when taken in the form of a supplement, L-tryptophan can interact adversely with fluoxetine. Typical symptoms include nausea and vomiting, agitation, anxiety and restlessness, headache, dizziness and increased perspiration. Individuals taking fluoxetine should avoid the use of L-tryptophan supplements without consulting the prescribing physician and/or a nutritionally trained healthcare professional. Apparently this response has never been elicited when fluoxetine has been combined with a protein-rich diet containing significant levels of L-tryptophan.⁴

Avoid supplements containing tryptophan or 5-HTP.The adverse reactions include the "serotonin syndrome", cardiovascular complications, extrapyramidal side effects such as akathisia, dyskinesias, and parkinsonian-like syndromes and an apparently increased risk of suicidality. Fluoxetine-induced mania and hypomania, seizures and sexual disorders are evaluated along with minor symptoms of allergic reactions, stuttering, hematological changes, psoriasis, and inappropriate secretion of the antidiuretic hormone. The major fluoxetine-drug interactions involve the amino acids L-dopa and L-tryptophan, anorexiants, anticonvulsants, antidepressants, anxiolytics, calcium channel blockers, cyproheptadine, lithium salts, and drugs of abuse.

Andi's Note: Naturally occurring tryptophan is important to eat when taking Prozac since it promotes the body's ability to produce serotonin. Food sources of tryptophan include red meat, dairy products, nuts, seeds, bananas, tuna, shellfish, quinoa and turkey. Shrimp, Crimini mushrooms, turkey and mustard greens are among the largest sources. See: WHFoods: tryptophan for complete details.
Vitamin B6 is necessary for the conversion of tryptophan to both niacin and serotonin.

Possible side effects
This video shows a calm, intelligent description of the possible dangers: http://www.ihealthtube.com/aspx/viewvideo.aspx?v=b3750aff0ff9aed9

My reaction to the video:Permanently alters the brain: YES, that is our goal with Prozac. Even after our kids stop taking it, the new dendrites will still be there.Addictive: As he explained, IF the patient is NOT properly nourished with foods that promote serotonin production (such as naturally occurring tryptophan), addiction can occur under certain circumstances. He also explained that this probably won't happen if doses are kept low, as ours is. People looking to SSRIs to help with depression may have a greater chance of experiencing this. Our kids don't take it for depression. Therefore, there is no need to look to raise the dose (except as their weight increases.)
Zoloft/Paxil are TERRIBLY addictive because, as he said, it's out of the body in a couple of days so the patient comes crashing down since their bodies don't have enough time to adjust to the lack of serotonin. The withdrawals are scary and can last for a week. (I know because I experienced this.)
Prozac stays in the body a long time afterward so the patient doesn't feel that crash. (I know because I experienced this.)
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Prozac May Stunt Growing Bones

Please note that low-dose fluoxetine hydrochloride (5 mg/kg)-treated (LOW); and high-dose fluoxetine hydrochloride (20 mg/kg)-treated (HIGH). Fluoxetine hydrochloride (Sigma-Aldrich, Inc.) was chosen as the SSRI for use because it has been shown to have a favorable risk-benefit profile in children and adolescents
The CMF protocol suggest 1 mg up to 20 mg, depending on age. vs. the 20 mg for every 2.2 lbs that they used in the following study:

Related Health News

By E.J. Mundell
HealthDay Reporter

THURSDAY, Nov. 11 (HealthDayNews) -- The success of Prozac in easing depression in children may come at the price of impaired bone growth, suggests a study in mice.

Researchers say cellular mechanisms important to bone growth may shut down in the presence of the drug, hindering healthy skeletal development. Growing mice exposed to Prozac for even a few weeks averaged 9.4 percent less bone formation in their thighbones compared to unexposed mice, the researchers report.

"This is a mouse study, however, and I wouldn't take people off Prozac based on just this study," stressed lead researcher Stuart Warden, an assistant professor of physical therapy at Indiana University School of Medicine. "Still, as a researcher, I would start to think about planning trials to address this in a clinical population."

In a statement, representatives from Eli Lilly & Co., the makers of Prozac, said "the findings warrant consideration, and should be placed in the context of the established record of safety and efficacy of fluoxetine [Prozac] in humans."

The study is published in the November issue of Endocrinology.

Prozac is just one of a family of antidepressants called selective serotonin reuptake inhibitors (SSRIs), which also include Celexa, Paxil and Zoloft. All of these drugs interact with nerve cells to increase production of the neurotransmitter serotonin, which is low in people with depression.

However, researchers recently discovered that 5-HTT -- a serotonin transporter molecule that is key to this process -- is also found in cells responsible for building and maintaining bone.

"If you have serotonin around these cells and these cells have receptors, serotonin actually influences the activity of those bone cells," Warden explained.

Using the same logic, his team theorized that serotonin-targeted SSRI drugs such as Prozac might also affect bone development.

To find out, they first examined bone growth in mice genetically engineered to lack functioning 5-HTT serotonin transporters in bone cells. A shutdown of this transporter "would be similar to being on lifelong Prozac, Zoloft or any other SSRI," Warden explained.

Compared to normal mice, these animals had bones that were between 6 percent to 13 percent narrower on average. Their bones were also weaker and less dense.

The researchers then shifted their focus to short-term Prozac exposure, giving young, growing mice daily injections of either low- or high-dose Prozac, or placebo, for four weeks.

"When we gave Prozac to really young mice that were still rapidly growing, it reduced the amount of bone they gained," Warden said. "It reduced their bone growth -- not how long the bones were, but how wide, and how thick."

Compared to unexposed mice, young mice exposed to relatively high doses of Prozac displayed a 6 percent and 9.4 percent reduction in bone formation in their spines and thighbones, respectively, according to the researchers.

Warden stressed that the study focused on Prozac because it is the sole SSRI currently granted U.S. Food and Drug Administration approval for use in children. He believes other SSRIs would have similar effects on bone.

"There's no reason to believe Prozac is unique here," Warden said.

For their part, representatives at Lilly said the study is far from conclusive. They point out, for example, that mice exposed to Prozac were somewhat less active than unexposed mice, offering an alternate explanation as to differences in bone mass.

They also defended Prozac's safety record. "Lilly has sponsored five clinical trials of Prozac in children, and all have been published in independent, peer-reviewed journals," the company said in a statement. "The safety and efficacy of Prozac is well-studied, well-documented, and well-established."

But Warden believes that larger clinical trials are warranted. He pointed to studies in adults that linked long-term SSRI use with an increased risk for hip fracture, as well as reduced bone mineral density in the neck and spine.

Prozac has already faced intense public scrutiny recently, following reports suggesting that it and other SSRIs might raise suicide risks in children.

"The main point of our study is not to induce panic in people on these drugs, but to highlight that further research is necessary," Warden said. "We need to have independent studies looking at these drugs, so things aren't brushed under the carpet."

More information

For the latest on the risks and benefits of antidepressant use by children, go to the U.S. Food and Drug Administration.

SOURCES: Stuart Warden, Ph.D., assistant professor, physical therapy,
Indiana University School of Medicine, Indianapolis; statement, Eli
Lilly & Co., Indianapolis; November 2004 Endocrinology
Copyright ©2004 HealthDay. All Rights Reserved.
This is a story from HealthDay, a service of ScoutNews, LLC.-------------

Antidepressants Linked to Thicker Arteries

Antidepressant use has been linked to thicker arteries, possibly contributing to the risk of heart disease and stroke, in a study of twin veterans. The data is being presented Tuesday, April 5 at the American College of Cardiology meeting in New Orleans.

Depression can heighten the risk for heart disease, but the effect of antidepressant use revealed by the study is separate and independent from depression itself, says first author Amit Shah, MD, a cardiology fellow at Emory University School of Medicine. The data suggest that antidepressants may combine with depression for a negative effect on blood vessels, he says. Shah is a researcher working with Viola Vaccarino, MD, PhD, chair of the Department of Epidemiology at Emory’s Rollins School of Public Health.

The study included 513 middle-aged male twins who both served in the U.S. military during the Vietnam War. Twins are genetically the same but may be different when it comes to other risk factors such as diet, smoking and exercise, so studying them is a good way to distill out the effects of genetics, Shah says.

Researchers measured carotid intima-media thickness – the thickness of the lining of the main arteries in the neck -- by ultrasound. Among the 59 pairs of twins where only one brother took antidepressants, the one taking the drugs tended to have higher carotid intima-media thickness (IMT), even when standard heart disease risk factors were taken into account. The effect was seen both in twins with or without a previous heart attack or stroke. A higher level of depressive symptoms was associated with higher IMT only in those taking antidepressants.

“One of the strongest and best-studied factors that thickens someone’s arteries is age, and that happens at around 10 microns per year,” Shah says. “In our study, users of antidepressants see an average 40 micron increase in IMT, so their carotid arteries are in effect four years older.”

Antidepressants’ effects on blood vessels may come from changes in serotonin, a chemical that helps some brain cells communicate but also functions outside the brain, Shah says. The most commonly prescribed antidepressants are selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac), which increase the level of serotonin in the brain. Other types of antidepressants also affect serotonin levels, and antidepressants can act on other multi-functional brain chemicals such as norepinephrine.

In the study, researchers saw higher carotid IMT in both participants who used SSRIs (60 percent of those who took antidepressants) and those who used other types of antidepressants.

Most of the serotonin in the body is found outside the brain, especially in the intestines, Shah notes. In addition, serotonin is stored by platelets, the cells that promote blood clotting, and is released when they bind to a clot. However, serotonin’s effects on blood vessels are complex and act in multiple ways. It can either constrict or relax blood vessels, depending on whether the vessels are damaged or not.

“I think we have to keep an open mind about the effects of antidepressants on neurochemicals like serotonin in places outside the brain, such as the vasculature. The body often compensates over time for drugs’ immediate effects,” Shah says. “Antidepressants have a clinical benefit that has been established, so nobody taking these medications should stop based only on these results. This isn’t the kind of study where we can know cause and effect, let alone mechanism, and we need to see whether this holds up in other population groups.”

In addition to Prozac, Jett also takes his curcumin everyday, which helps support his heart. His last heart check up showed a perfectly healthy heart, in size, shape and function. He will have another cardio evaluation in June. Will update then.
June's evaluation revealed a perfect heart, but the cardio sees signs of possible pulmonary hypertension. I'm looking into treatment and causes. I'm considering adding CoQ10 for support.

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The Robert W. Woodruff Health Sciences Center of Emory University is an academic health science and service center focused on missions of teaching, research, health care and public service.

Possible Side Effect: Tardive Dyskinesia

Tardive dyskinesia is a movement disorder caused by long-term use of certain medications called neuroleptic drugs, along with some other drugs that increase the brain's sensitivity to the neurotransmitter dopamine. It is characterized by uncontrolled facial movements such as protruding tongue, chewing or sucking motions and making faces.
Tardive dyskinesia is a very serious side effect of antipsychotic medications in particular, and patients taking such drugs should know what to watch for. Drugs that can cause tardive dyskinesia are mainly antipsychotic medications and include:

• Abilify (Aripiprazole)
• Clozaril (Clozapine) (may also treat the condition)
• Geodon (Ziprasidone)
• Haldol (Haloperidol)
• Loxitane / Loxapac (Loxapine)
• Mellaril (Thioridazine)
• Navane (Thiothixine)
• Orap (Pimozide)
• Piportil (Pipotiazine)
• Prolixin / Modecate (Fluphenazine)
• Risperdal (Risperidone)
• Serentil (Mesoridazine)
• Seroquel (Quetiapine)
• Stelazine (Trifluoperazine)
• Thorazine (Chlorpromazine)
• Trilafon (Perphenazine)
• Zyprexa (Olanzapine)

Some of the non-neuroleptic drugs that may also cause tardive dyskinesia are:

• Asendin (Amoxapine)
• Cocaine and other street drugs
• Elavil (Amitriptyline)
• Lithium
• Nardil (Phenelzine)
• Prozac (Fluoxetine)
• Sinequan (Doxepine)
• Tofranil (Imipramine)
• Zoloft (Sertraline)

Ironically, the neuroleptic drugs are dopamine antagonists, meaning they block dopamine receptors on nerve cells. However, over time this can cause the brain to compensate by creating more dopamine receptors and making them more sensitive, leading to serious side effects.

Symptoms of Tardive Dyskinesia
 
Tardive dyskinesia is characterized by repetitive, involuntary, purposeless movements such as:

• Fine, worm-like movements of the tongue
• Lip smacking
• Chewing or sucking movements
• Grimacing (making faces)
• Puckering or pursing the lips
• Tongue protrusion
• Rapid eye blinking

There may also be uncontrolled movements of the arms, legs and body. According to an article at Wikipedia, "Impaired movements of the fingers may appear as though the patient is playing an invisible guitar or piano."

Prevention, Treatment and Outlook
Prescribing physicians should attempt prevention by prescribing the lowest effective dose of these medications for the shortest possible time. After a diagnosis of tardive dyskinesia, decreasing dosage or discontinuing the problem drug(s) may solve the problem, or it may cause symptoms to worsen. If they do get worse, they may eventually go away, or they may continue indefinitely. Thus, it is important to get an early diagnosis if you suspect you or a loved one is exhibiting symptoms of this disorder.
A number of medications have been used to try to control the symptoms of tardive dyskinesia, including Clozaril (clozapine), Botox (botulinum toxin), benzodiazepines such as Klonopin (clonazepam), and several others. Treatment is not always successful.

Andi's Note: It's theorized that increasing dopamine intake may help to offset this side effect. Non-pharmaceutical ways to increase dopamine are:

NADH (an activated form of niacin..B3)
Mucana Pruriens....an herb
Phenylalanine
Tyrosine

Jett takes 100mg of tyrosine every morning.
I do know of some children who have this side effect from Prozac's use. One child felt like a "purring kitten" in her mother's arms. Her movements stopped after discontinuing Prozac. Another child had a lot of the other movements such as teeth grinding and lip smacking. This child used Prozac for 5 years.

References
Brasic, J.R. (2006). Tardive Dyskinesia. Retrieved July 30, 2006 from http://www.emedicine.com/neuro/topic362.htm.
National Institute of Neurological Disorders and Stroke. (2006). NINDS Tardive Dyskinesia Information Page. Retrieved July 30, 2006 from http://www.ninds.nih.gov/disorders/tardive/tardive.htm.
Periut, P. (2005). Tardive Dystonia. Retrieved July 30, 2006 from http://www.emedicine.com/med/topic620.htm.
Wikipedia. (2006). Tardive Dyskinesia. Retrieved July 30, 2006 from http://en.wikipedia.org/wiki/Tardive_dyskinesia.

Source: http://bipolar.about.com/od/sideeffectslibrary/f/tardivedyskines.htm

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Weight gain in infants breastfed by mothers who take fluoxetine.

Chambers CD, Anderson PO, Thomas RG, Dick LM, Felix RJ, Johnson KA, Jones KL.

Departments of Pediatrics, University of California, San Diego, California 92103, USA. chchambers@ucsd.edu

OBJECTIVE: Despite the manufacturer's recommendation that fluoxetine not be used by women while breastfeeding, many women choose to do so. There is little information available in the literature to suggest that this practice is or is not safe. The purpose of this study was to examine weight gain in infants who are breastfed by mothers who take fluoxetine, compared with weight gain in infants who are breastfed by mothers who do not take any psychotherapeutic medication. A secondary goal was to assess the frequency of reported side effects in infants who are breastfed by mothers who take fluoxetine. METHODOLOGY: A retrospective cohort study design was used. Subjects were identified from an ongoing pregnancy outcome study conducted through the California Teratogen Information Service and Clinical Research Program. A total of 64 women were interviewed who had taken fluoxetine during a pregnancy between the 1989 and 1997; 26 of these women breastfed their infants and continued to take the medication, and 38 breastfed their infants but did not take the medication. Postnatal weight gain was taken from pediatric records, and the frequency of side effects was measured by maternal response to the interview questionnaire. RESULTS: Using linear regression analysis, the infants who were breastfed by mothers taking fluoxetine demonstrated a growth curve significantly below that of infants who were breastfed by mothers who did not take the drug. The average deficit in measurements taken between 2 weeks and 6 months of age was 392 g (95% confidence interval: -5, -780). Using a repeated measures analysis of covariance for those infants with more than one postnatal weight measurement available, the difference between the two groups was similar, approximately 1.2 standard deviations (P =.005). In response to interview questions regarding side effects, no mother who breastfed her infant while taking fluoxetine reported any unusual symptoms that could be attributed to the medication. CONCLUSIONS: These data do not suggest that women who breastfeed while taking fluoxetine are likely to note unusual behavior in their infants that they consider related to use of the medication. However, although there was no excess of infants in the fluoxetine group with postnatal weight measurements >2 standard deviations below the mean, these data indicate that breastfeeding while taking fluoxetine is associated with reduced growth that may be of clinical importance in situations in which infant weight gain is already of concern.

PMID: 10545587 [PubMed - indexed for MEDLINE]

Andi's note: Weight gain has been a constant battle for Jett. The first month and a half, he was considered Failure to Thrive, off and on, but I was able to get him up to the 50% in time for his heart surgery at 6 months.
Jett has gained only two pounds and lost one pound in the 10 months since heart surgery (age 6 to 16 months). He's been on Prozac from age 10-16 months. I haven't seen a change in his appetite, but it certainly hasn't improved on Prozac! His BMI indicates that he is underweight for his height at 13%. On the typical growth chart, his weight is well below 0%, on the DS growth chart, his weight is below 10%. I feed him full fat foods including butter, avocado and coconut oil. He still is mostly breastfed, but I offer him solid food throughout the day. He enjoys eating whatever food I eat, but just doesn't eat much of it. He is full of energy and sleeps well.

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