Some of the most interesting – on a pharmacological level – medications I’ve encountered are cancer treatments.

Take Tamoxifen, for instance.  This highly effective treatment for certain types of breast cancer works because it blocks the effects of estrogen in the breast.  Since estrogen plays a role in getting cells in the breast to grow, this has significant anti-cancer effect.

Yet there is a downside.  Tamoxifen acts like estrogen in the uterus, which increases risk of uterine cancer over time.

I love analyzing medications and that extends to cancer treatments.  But it is a more challenging interest than for other treatments.

When I look at an asthma medication, things are simpler.  Does it improve breathing?  Does it reduce the need to go to the emergency room?  Things get thorny when common medications have black box warnings, but still not too hard.

Cancer medications are challenging on many levels, intellectually, emotionally.  You are confronted with statements like “those on medication X lived 6 months on average, while those on placebo lived 4 months on average.”

The best part is finding new treatments that offer hope.  Even then I am weighed down by knowledge (or, more accurately, lack of knowledge) and the challenge of grappling with exceptionally complicated information.

Take the aromatase inhibitors.  Some studies say that they are a better treatment in post-menopausal woman than tamoxifen for preventing breast cancer from coming back.

The aromatase inhibitors were so much better that a study I look at was actually stopped to give participants the opportunity to switch to them.

That’s wonderful, right?

Yes.  That said, one study I looked at showed superiority of the aromatase inhibitors in preventing breast cancer recurrence but showed an increased rate of other cancers.

Let me end this post with some thoughts on where cancer treatments are going.

Future Cancer Therapies

The goal of future cancer treatments is to find the molecular pathways that are deregulated in cancers and target them alone.  Think doing a targeted missile strike on a house instead of carpet bombing a city.

The limitations to targeted treatments include the sheer complexity of cancers.  You can knock out one pathway that leads to cancer formation only to have the tumor adopt another approach.  Cancer doesn’t form when just one thing goes wrong, rather it happens when many things go wrong at once.

Resistance often arises.  Cancerous cells are full of nasty tricks, like developing pumps that get rid of the medications you throw at them called Multiple Drug Resistance pumps.

New cancer treatments for the past few years have tended to fall into two categories.  There are the tyrosine kinase inhibitors which are almost all named something that ends in “nib” (Lapatinib, Gefitinib, and Sunitinib).  Then there are the monoclonal antibodies that have extreme specificity to some molecular target.

The tyrosine kinase inhibitors try to stop specific pathways associated with the development of cancer.  Tyrosine kinases are a fairly large family of receptors and play a very large role in the regulation of cell growth.  Their efficacy can range from phenomenal, Gleevec, to disappointing, Gefitinib.

The monoclonal antibodies have a variety of targets but all try to knock out some key aspect involved in the cancer.  Herceptin, for instance, binds to HER2 receptors that are highly overexpressed in a significant percentage of breast cancers.  Avastin binds to VEGF, a messenger that tells blood cells to grow, feeding the cancer.

There are additional areas being investigated.  While unlikely to be used for at least several years, PARP inhibitors may play a role in treatment of breast cancer by increasing cells susceptibility to traditional chemotherapy.

As follows, here is a list of new cancer drugs that show especial promise.

Herceptin or trastuzumab is a monoclonal antibody to the HER2 receptor and a recent innovation in breast cancer treatment.  In those who have the mutation specific to it, Herceptin can work impressively well.  At $100,000 per year of treatment, however, it comes at a cost.

Sutent or Sunitinib is an interesting new medication that disrupts the activity of multiple tyrosine kinases.  More non-specific than many other similar medications, it has shown significant efficacy for treating renal cancer as well as a back-up for gastrointestinal stromal cancer.

Erbitux is an antibody to the epidermal growth factor (EGF) receptor, which means it has similar activity to other medications discussed here.  It may play a role in treating colorectal cancer and was recently discovered to increase by 20% objective survival when used in head and neck cancers, the first successful, new treatment in 30 years.

Arimidex and Femara are members of the aromatase inhibitors.  Very recent studies have shown their superior efficacy to the traditional treatment of tamoxifen for preventing breast cancer recurrence in post-menopausal women.  Best of all, Arimidex is about to go off patent.  That said, it is important to note that we do not know as much as we’d like about their long term side effects compared to tamoxifen.

Tarceva or erlotinib is a new treatment for non-small cell lung cancer.  It is a tyrosine kinase inhibitor that is fairly specific for the epidermal growth factor (EGF) receptor.  In terms of efficacy, however, it is not that great.  It may work best in patients who have a mutation in the EGF receptor, which may mean genetic tests to guide use.

Olaparib is a PARP inhibitor that works to prevent cells from repairing damage to their DNA.  (Note that it’s not a nib).  As many chemotherapies work by causing DNA damage in some form, this medication may increase the efficacy of traditional treatment.  Olaparib is being especially investigated for use in women with BRCA1 or 2 mutations who have more aggressive cancer than normal.

Gleevec or imatinib is commonly viewed as one of the most exciting new medications because it is highly effective for treating CML, chronic myeloid leukemia, as well as possibly other cancers.  Gleevec was hailed as a victory for scientific research because it was discovered by systematically screening chemicals for effectiveness in targeting cancer-related pathways.

While CML is somewhat rare, Gleevec comes at a very high cost, raising the question of corporate greed.

Sutent – an exciting new cancer treatment

Sutent, generic sunitinib, is a new cancer medication that has quickly become accepted as a first line treatment for renal cell carcinoma (RCC) as well as a treatment for gastrointestional stromal tumor (GIST) after resistance to imatinib develops.

It is being investigated for other uses as well, like for treating breast cancer.

Sutent is a tyrosine kinase inhibitor and acts on multiple sites.  This is important because dysregulation of tyrosine kinases is a common factor in the development of cancer as they play a major role in regulating cell proliferation.

Sutent seems to have especial impact on tryosine kinases mediated by Von Hippau Lindau factor, which is involved in release of factors like VEGF, EGF, and other cancer favorable factors.  Abnormalities in that pathway are often associated with renal cell carcinoma.

Other factors Sutent may play a role in lowering activity of include PDGF and fetal liver tyrosine kinase receptor.

This diverse spectrum of effects may make Sutent a useful treatment for different types of cancer.  On the other hand, it also means that side effects are somewhat more common on it than similar medications.

Sutent for Renal Cell Carcinoma

The standard treatment for renal cell carcinoma (RCC) has been a combination of interferon-alpha and interlukine-2.  These are both messengers that the body has already, and by providing them, you hope to prompt the body into a strong response against the tumor.  We’ve been forced to use that treatment because standard chemotherapies, unfortunately, do not work that well as this type of cancer is highly resistant.

It doesn’t work that well, with only 10-20% response rates.

A recent study that compared Sutent to standard therapy showed a superior 11 months of time for disease progression compared to 5 months for those treated normally.  This study additionally also showed a significant survival benefit.

One study that looked at Sutent use in those who failed or were not eligible for cytokine treatment showed a significant 40% primary end point response with some shrinkage in almost everyone.  That said, 33% had disease progression at 3 months.

Sutent for Gastrointestional stromal tumor

For this type of tumor, the typical treatment has been imatinib, a related medication that also is highly effective.  Resistance, however, tends to develop with time, and researchers wondered if Sutent might be effective as a back-up option.

The studies have again been fairly positive.

A recent study that compared Sutent to no treatment in this use was stopped in the middle because of how effective it was.  Those who were using Sutent had roughly 27.3 weeks before their disease progressed, compared to only 6.4 weeks for those using standard treatment.

On the basis of this and other studies, sunitinib has become a standard backup treatment for GIST when imatinib stops working.

Sutent Side Effects

The side effects of Sutent are significant and common.  In one study in treating RCC, everyone had some sort of side effect.  Remember, Sutent is fairly non-specific.  That means it effects many other tissues beyond the cancer.

Sid effects include neutropenia and lymphopenia, or depletion of certain types of immune cell.  Alopecia, hair loss, or hair color change is not uncommon.  Other common side effects include headach  and asthenia, or loss of strength.

Somewhat rarer are hypertension and rash,

Use of Sutent may cause electrolyte imbalances including hypokalemia.

Sutent dosing

The standard treatment plan is to use 50mg per day for 4 weeks, with two weeks off.  And so on.

Other medication dosing options being explored include 50mg daily for 2 weeks with one week off.  Additionally, it may be possible to take 37.5mg as a continuous daily dose.

As always, follow your doctor’s instructions.

Miscellaneous

Sutent is metabolized by the CP450 3A4 system and may interact with other medications that use that pathway.  The drug does not seem to be significantly effected by the foods you consume.

Strattera or Atomoxetine is a new treatment for ADHD that was approved in 2002 and the first medication approved for treating ADHD in adults.

It is a norepinephrine reuptake inhibitor, which means that, like Ritalin and the stimulants, Strattera increases the level of norepinephrine that cells are exposed to.

This hopefully results in increased attention, focus and motivation – reducing the symptoms of ADHD.

Unlike the stimulants, however, Strattera takes up to 8 weeks to work.  The exact reason for this delay is unclear, but it is reminiscent of behavior more typical of an antidepressant.

The main benefits: Strattera provides full day coverage with one or two doses, is not a stimulant, and is hard to abuse.  May work when stimulants don’t or are not a good idea.

The main disadvantages: Strattera isn’t as effective as the stimulants, is expensive, and takes a while to start working.  Plus it has its own array of side effects.

Efficacy:

Strattera is definitely better than placebo at treating the symptoms of ADHD.  Beyond that, however, the studies have been modestly positive.  In one study, for instance, of several hundred people treated for 10 weeks, scores on the AISR scale went from an average of 38.5 to 24.5 for those treated with Strattera.

The AISR scale consists of 18 questions each rated on a scale of 0-3, where 3 is most severe and 0 is not significant.  The max score is 54.  As such, a reduction from 38.5 to 24.5 is fairly impressive.

Unfortunately, the placebo treated group went from an average of around 39.2 to 28.9.

The difference between Strattera and placebo of 4.4 means that a few questions were answered as less severe than originally.  So there is an effect, and it is positive, but it is not as significant as with the stimulants.  Strattera shows similar if slightly better efficacy in other studies.

Roughly 25% of people who use Strattera stop specifically because they feel it does not work well.

Dosing:

Strattera is typically started at .5mg/kg and raised to 1.2mg/kg for a maximum of 100mg per day in adults.

As it is digested by the CP 450 system, medications such as Prozac may interfere with Strattera.

Strattera Side effects:

Anywhere from 10-25% of people report side effects as a reason for stopping Strattera.  They are mostly mild.  That said, over several years of use, the risk of having some sort of serious side effect becomes not insignificant.

People who use Strattera typically lose a small amount of weight.

Most common:

>50% report headaches, some issues with digestion, nausea or upset stomach, and sleepiness

~13% report abdominal pain

Some studies report increased rates of vomiting and constipation on Strattera.

~5% report dry mouth, urinary hesitation, erectile dysfunction

Less common side effects:

Low but possibly increased rates of sinusitis, impaired digestion,

Depression, thoughts of suicide (in one study, 11/714 had suicidal thoughts, or 1.5%), appendicitis.  New aggression or irritability is not common but not uncommon side effect of Strattera.

Rarest side effects:

Heart murmur, prolonged QT on ECG, liver issues, upper abdominal pain, diabetic ketoacidosis

This list is not complete; see manufacturers insert for more.

Use:

Most people who use Strattera have tried stimulants in the past and had adverse reactions or preferred to try a different medication.  Stimulants generally don’t work in about 30% of people with ADHD who try them.  Additionally, in some groups, stimulants are contraindicated.

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Zoloft vs Prozac

Everyone’s heard of these two drugs.  They’re that popular.  But what are they?  How do they compare?  And in the analysis of Zoloft vs Prozac, which comes on top?

Zoloft might have a slight advantage over Prozac.  Yet they both can have serious side effects, and don’t always work.

For a discussion about the pros and cons of antidepressants, you may be interested in reading a balanced approach to antidepressants.

Let’s start at the beginning.

Zoloft

Zoloft was discovered during the 70s/80s by accident.  A team at Pfizer was researching compounds for a condition not related to depression.  One of those, what would later become Zoloft, had impressive selective serotonin reuptake inhibitor (SSRI) effects.  Against the wishes of higher management, the team pushed for the development of the medication.

Initial approval of Zoloft almost didn’t happen.  The FDA was concerned about the poor efficacy of the medication, and by the improper design of the studies.  Zoloft didn’t seem to work well, and the studies that showed that were not examples of good science.  Yet they gave it the green light.

Within 15 years, it would become the most popular antidepressant, with 29 million prescriptions in 2007.

Prozac

Prozac was one of the first SSRI medications altogether.  It was discovered slightly before Zoloft.

It’s entry to the market changed how depression is treated.  The earlier medications, the MAO inhibitors and Tricyclics, had very significant and serious side effects.  It seemed at first that Prozac was much safer.  And it worked about as well.

In 2007, 22 million prescriptions were filled for fluoxetine, the generic form of Prozac.

Comparison of Prozac vs Zoloft

Both work in about the same time span, of 4-6 weeks.  Both should be taken once daily, and the difference in doses aren’t important.  Both have some benefit in 50-70% of those who take them.

Crucially, they are both SSRIs, and they both work by almost the same mechanism.  This means that they aren’t really that different (and this is also true for many other antidepressants like Paxil).

Some analysis of many, many patients showed slight superiority in Zoloft’s efficacy for treating depression.  One paper put it the difference between the two that Prozac is certainly not better than and probably not worse than Zoloft.

The main difference between the two may be in side effects.  One study analyzing Zoloft vs Prozac found that Prozac had slightly less “retardation,” or feeling of being slowed down.  The same study, however, showed that Prozac might have more anxiety and irritability.

On the other hand, diarrhea is more associated with Zoloft than Prozac.

They both have similar rates of sexual dysfunction, and similar rates of physical addiction.  And they both tend to cause significant weight gain.

Remember

Antidepressants are very hit and miss.  They often don’t work, and it’s possible that a lot of their effect is from placebo.  They are powerful medications and have been shown to double the risk of suicidal thinking in some analysis.  Because they have significant side effects, a high percentage of people taking them stop shortly after starting.

That said, they can also be life-changing.  For some people, they can make normal living possible.  As always, the key is to balance the potential benefits against the potential harms of a treatment.

Related Articles:

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2. Weight Gain from Zoloft and Prozac
3. 10 Ideas to Treat Resistant Depression
4. The Top 5 Depression Songs
5. Ethical Issues in Health & Medicine

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Concerns about Actos

You may be considering pioglitazone or Actos to help treat your diabetes.  But you absolutely need to know that Actos has some very serious side effects and that it’s not entirely clear how well it works.

Pioglitazone, or Actos, is a very popular treatment for Type 2 Diabetes, with prescriptions counting for about 20-25% of total.  It works on peroxisome proliferator activated receptor-gamma receptors to improve sensitivity to insulin in various parts of the body.

The good thing is that Actos does have some benefits.  It seems to lower blood pressure, and seems to have a positive effect on certain important markers of health, like urine composition and levels of lipids in the blood.

And some studies like PROactive have shown that it has significant benefits in lowering risk of mortality from certain aspects of diabetes.

Concerns

First, the way that PROactive measured its outcomes was not properly done and changed in the middle of the study, almost certainly to make the medication come off as being better.  And most of the other studies don’t clearly show health benefits.

Yes, Actos or Pioglitazone does seem to have significant effect on certain physiological factors.  But those measures don’t necessarily translate to improved life-span or reduced risk of events.  And even the PROactive study didn’t have statistically different outcomes for certain serious diabetes related problems.

One analysis of 22 studies argued that 21 of them showed only improvement in surrogate measures.  That means that the medication was shown to have some sort of physical effect but not necessarily have health benefits.

Heart Failure

Worse.  Pioglitazone might significantly increase the risk of heart failure.  In one study, rate of heart failure went up from 2% to 4%, and in another from 8% to 11%.  This is despite having some effects that are good for the heart, like reducing thickness of certain arteries.

Actos also increases risk of bone fracture, and, like a related medication that was withdrawn from the market, may have significant liver toxicity.

Thoughts

Because of these factors, and the lack of definitive and convincing long-term studies focused on measuring health end-points, Pioglitazone’s cost-benefit analysis is not clear.  Its use over other options for Diabetes management should be very carefully considered.

Thanks for reading!

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Metformin, brand name Glucophage

You may be taking or considering metformin if you have Type II diabetes, “prediabetes,” or, though the scientific evidence for its use isn’t so solid, polycystic ovary syndrome.

Metformin works in several ways. It helps certain parts of the body respond properly to insulin, reduces how much glucose is released into the bloodstream, and does a few other things.

Most of what we know about Metformin is good. It doesn’t seem to cause weight gain, and in fact, may cause slight weight loss. It’s affordable. And it has 4 decades of use, meaning we know a lot more about it than many other medications.

One study showed that use of metformin over several years reduced mortality – or death - rates related to diabetes by an impressive 36%.

Side effects of metformin

Metformin’s side effects are mostly mild and treatable, though there is a the rare chance of a problem called lactic acidosis. About 30% of users experience some sort of side effect, including indigestion and diarrhea.

Taking metformin with a meal is one way to reduce problems, as well as taking an extended release version. The immediate release form has about a 17% rate of diarrhea, for instance, while the extended release has only about 8%.

Some have complained that metformin makes them smell bad.

Lactic acidosis is a very rare side effect that is fatal about 50% of the time. Estimates of how often it occurs range from 1/30,000 patient-years to a bit higher.  But assuming you meet the criteria for using metformin, most likely you shouldn’t worry about it.

Most doctors strongly feel that the benefits of metformin outweigh the risks of lactic acidosis.  As one doctor puts it, “Of 10,000 diabetic patients treated for 10 years with metformin, only 10 will die from lactic acidosis. [Based on a large study] of those 10,000 patients… metformin would [have prevented] 500 diabetes related deaths.”

Because of how effective metformin seems to be, some doctors argue for more aggressive use of the medication than is currently done.

Most common metformin side effects: nausea, metallic taste in mouth, some weight loss, vomiting and abdominal bloating.  Cramping or a feeling of fullness is also fairly common.

Talk to your doctor: if you feel excessively weak, have heartbeat changes or irregularities, chest pain, or signs of an allergic reaction.  Some people experience hypoglycemia, or too low blood sugar, on Metformin, which is also important to watch for.  Signs include chills, weakness and dizziness.

You may need to stop use if you are going to get an X-ray or scan that involves injection of die into your body.

This list does not include everything; see manufacturer’s insert for more.

Notes

Metformin can cause Vitamin B12 and folic acid deficiencies, so make sure to be eating a well balanced diet.  Additionally, remember that the initial and ideal treatment for type II diabetes is exercise and improved diet.

And it’s important to take metformin as your doctor directs.  It takes a while to start working and needs to be taken as recommended.

There are several conditions which mean you shouldn’t take metformin, like kidney problems. It’s possible that a significant amount of the lactic acidosis occurs in people who, according to the strict guidelines, shouldn’t have been taking the medication.

Related articles:

1. Bydureon Diabetes Drug, Side Effects
2. 10 Tips for Living With Type 1 Diabetes
3. What are the symptoms of Diabetes?

Just for fun:

1. 20 Fun Facts About Alcohol
2. The 10 Worst Diseases Ever

1) 1/10 people in America are currently taking an antidepressant (AD)

2) Michael Jackson was reportedly taking Zoloft and Paxil when he died.  Antidepressants have been shown to contribute to heart disease.

3) Luvox was being taken by a shooter in the Columbine High School shootings.

4) We have no idea how antidepressants actually work

5) Effexor’s side effects include vomiting and nausea, while Zoloft is associated with diarrhea

6) Almost all of the new ADs work similarly well (or badly) – the only significant difference is what side effects they have

7) ADs can cause extreme anger in some people, and there are many lawsuits against AD drug companies for resulting violence

8) Prozac is the best recognized AD with the most references to it in music and popular culture

9) Anna Nicole Smith’s son was taking Lexapro when he died

10) Paxil is one of the hardests ADs to quit.

11) ADs can be extremely hard to quit.  Withdrawal, which is a very common problem, can involve “brain zaps” and general horrible feelings.

12) Some antidepressants work only 50% of the time.  Placebo?  That works about 30%.  Big difference?

13) Remeron has been linked to immune system failure

14) Antidepressants can cause suicidal thinking in children and perhaps adults

15) Celexa is used in autistic children who have OCD-like behavior, but it doesn’t seem to help

16) Antidepressants can possibly cause birth defects

17) Tricylcic antidepressants are poisonous and can be deadly if an overdose happens

18) The SSRIs (including Zoloft and Prozac) cause sexual dysfunction in most people who take them

19) Kids as young as two have been put on antidepressants

20) Wellbutrin very often causes extreme anxiety and can rarely make the taker lose touch with reality

21) Bonus: Women who take antidepressants are at a 45% increase risk of having a stroke.

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What did you think about this post?

Note: This is an editorial

Antidepressants – what’s going on?

One out of ten Americans are currently on antidepressants.  That’s just the beginning.  More than 25% of college students at some schools are on them.

Everyone is being given them for all sorts of reasons.  Are they really that effective or safe?  Maybe.  That said, there is a horrible secret.

We don’t know how antidepressants work.  We don’t know if they are safe for long term use.  And finally, we don’t know how well they work, and for what reasons they should be prescribed.

There’s too much money at risk for the big drug companies to bother to answer these questions.

After all, antidepressants are ideal money-makers, $80 billion annually.  They have to be taken daily for months if not years, and it can be impossible to tell if they’re working.  And they have serious side effects, like possibly doubling your risk of committing suicide.

Flawed studies

Everything we know about antidepressants comes from medical studies.  But the studies are really screwed up.

First, who runs the studies?  The drug companies.  What do they have at stake?

Good results mean that they make hundreds of millions of dollars.  Bad results mean they’ve wasted years of research and development.  What do you think happens?

Positive results in the studies are inflated on average 32%.  One analysis of 74 trials covering 12,500 patients showed that 36 studies gave negative results – and a shocking 11 of those were reported as being positive!  And if the negative studies can’t be spun positive, then we simply don’t hear about them.

Studies on antidepressant safety and efficacy are 94% positive – but if negative studies were published, they’d only be 51% positive.  The difference between what we hear and what is actually going is especially big for new drugs like Remeron.

The less time spent testing the drug means the less chance of picking up annoying side effects and saves operating costs.  Because of that, most studies don’t track long term use, and some studies last only a month.

That’s right.  Despite antidepressants being taken for months if not years, most research into them only goes on for a month or two, ignoring long term risks.

Extremely limited research

Millions of people take antidepressants.  By contrast, the studies which confirm their efficacy and safety study at most a thousand patients.

The initial studies for Prozac that approved its use had only a few hundred patients complete the study.

Some quick math.  30 million people have taken Prozac.  Now imagine there’s a serious side effect that occurs in 1/10,000 of the people who use it, and was missed in the initial studies.  That’s 3,000 people.

Antidepressants aren’t benign drugs, far from it.  They can cause thoughts of suicide in up to 4% of children, anger and violence in adults, alongside more mundane issues like nausea, restlessness and sexual dysfunction.

The Serotonin Hypothesis – a myth?

We don’t know how the medications work.  The Serotonin Hypothesis – that reduced levels of serotonin in the brain cause depression – is inaccurate and lacks scientific basis.

Lowering the level of serotonin in the brain doesn’t cause depression.  Increasing its levels directly doesn’t do much, either.  And if low levels of serotonin were to blame for depression, antidepressants wouldn’t take several weeks to work – they would work within days because that’s how fast they raise levels.

To cap it off, antidepressants that don’t target serotonin – like Wellbutrin – work at about the same rate as those that do.  Clearly the serotonin hypothesis is a vast over simplification that’s convenient for the drug companies.

Use in bipolar?

Antidepressants are very heavily used in patients with bipolar disorder.  Unfortunately, the data seems to be at best only moderately in support of such use, and there are no antidepressants approved for use in Bipolar (July 2008).

The STEP-BD, Systemic Treatment Enhancement Program for Bipolar Disorder, a study run by the National Institute of Mental Health, seems to show that antidepressants are only as effective as placebo for bipolar depression.

And while antidepressants aren’t much better than placebo for bipolar patients, they may exacerbate mood cycling.

Use for depression

A similar major study of antidepressant efficacy for regular depression, STAR*D, showed similarly lackluster results.

STAR*D’s data is open to interpretation, but at the least indicates that antidepressants are not as effective as thought.  About only 50% of patients experienced improvement initially, and over a year span efficacy was only about 25%.

For the vast majority of uses, antidepressants may work only as well as placebo, or a sugar pill.  Placebos, after all, show about the same 25% efficacy.  Due to the psychological nature of depression, the placebo effect absolutely must be monitored for.

Conclusion

Antidepressants do help some people, and do save lives.  A black-box warning in 2003 which sharply reduced their use may be linked to a significant increase in teen suicides.

But they are also huge money makers with highly inflated efficacy rates, and should not be as heavily prescribed as they are.  In many populations, they are no more effective than placebo, but unlike placebo have significant side effects.

Their use in Bipolar patients should be carefully examined.

You might like:

10 Ideas for Treatment Resistant Depression

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Sources:

Why antidepressants are not antidepressants: STEP-BD, STAR*D, and the return of neurotic depression
Effectiveness of antidepressants: an evidence myth constructed from a thousand randomized trials?
Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature
The Shocking Truth – Boston Magazine

Immediate Depression Relief

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Does your eye get irritated or feel dry?

Most older people have at least some experience with dry eye, a condition that can require treatment and disrupt quality of life.

Dry eye is caused by inadequate tear production or inflammation in your eyes.

If you don’t know what Restasis is, you probably want to skip to the Cylcosporine part. This is a friendship post (in response to a friends question).

What is Restasis?

Restasis is an eye drop treatment that primarily consists of Cyclosporine.  See later for a discussion of how Cyclosporine works.  Restasis’s effectiveness has been shown in multiple studies for treatment of various eye conditions like keratoconjunctivitis.

Its use for irritation from contact lenses has not been extensively studied, and it seems that typical eye drops may work just as well.  Before using Restasis make sure it is 1) approved for your indication and that it is 2) more effective than less powerful treatments, and that you don’t have any conditions that mean you shouldn’t take it.

Restasis tends to work.  Some studies show 15% significant improvement, while other studies show 72.1% of patients with dry eye getting better to some degree.  In general, it seems that most Restasis users experience improvement.  Patience is key, because it takes several months to achieve a therapeutic effect.

Side effects of Restasis are mostly mild and consist of eye burning or blurring.  This is in contrast to corticosteriods, another treatment, which do have serious side effects, as well as most systemic drugs which effect the whole body.

Because Restasis is applied to the eye, and tends not to penetrate into the body, it seems to be safe.  That said, there are indications like infection and herpes which you need to tell your doctor because it may not be an appropriate medication then.

Use patterns of Restasis are not entirely clear.  Most users are over 50 and women, and it’s typically one of the first treatments sought.  While the manufacturer recommends using 2 vials daily, most users end up using from .25 a vial to 1.25 vials daily, but if this provides adequate treatment has not been medically evaluated.

Important issues

Whether cyclosporine is carcinogenic is a hottly debated topic in medicine.  What about Restasis?

A cursory look at the 58 articles found in pubmed for the search “Opthalmic Cyclosporine Cancer” shows that none talk about the potential of Restasis to cause cancer.

Several, however, talk about the use of cyclosporine to treat retinoblastomas, a serious type of eye cancer.

It’s important to note that blindness and other serious events have been reported in association with bone marrow transplants and Restasis use.

What is Cyclosporine?

Cyclosporine is a substance produced by the fungus Tolypocladium Inflatum, and is a powerful medication used to prevent organ rejection after transplant.  If you’re giving someone else’s kidney or heart, for instance, it can help stop your body from launching an attack on the new and foreign body part.

Because of how it works, Cyclosporine can also help with dry eye.

Cyclosporine does at least two important things.  It changes how T cells interact with IL-2, reducing its effectiviness.  IL-2, or interleukin-2, is a messenger protein that tells your T-cells to replicate.  Because T-cells play a key role in immune reactions, suppressing their growth can reduce the inflammation in your eye.

Cyclosporine may also help keep your eye healthy and strong.  The way it does this is by preventing essential lining cells from committing apoptosis – or cellular suicide.  Cells tend to commit apoptosis if their local environment becomes a war zone, so to speak, with a continual immune reaction causing too much stress.  Keeping epithelial cells alive also helps prevent further degeneration.

Sources:

Topical Ophthalmic Cyclosporine: Pharmacology and Clinical Uses

Can Restasis Help Dry-Eye Contact Lens Wearers?

Topical ciclosporin in the treatment of ocular surface disorders