Ranking the Mood Stabilizers

RANKING THE MOOD STABILIZERS
(Intro to Mood Stabilizers)

1. ABILIFY
Abilify is an atypical, and is my top ranked mood stabilizer. It helps with agitation, irritability, mania and depression. It usually starts helping the first day taken. It comes in multiple size tablets, 5, 10, 15, 20 and 30mg. Because the tablets can be cut in half it makes for easy titration of dose. Abilify also has a long duration of action so it doesn’t hurt to be late or miss a dose. It also doesn’t matter whether you have eaten before taking.
Side-effects are mild. Occasionally there is restlessness in the first few days but that usually goes away. If restlessness is a significant concern, it is easily managed with Clonazepine, Ativan, or Propranolol. If sedation occurs it can be taken in the evening. There usually is no weight gain or sexual dysfunction.
Many of my patients feel that this medication more than any other mood stabilizer has significantly changed their life for the better. Even after 1 year or more it continues to work well and have negligible side-effects.

2. SEROQUEL
Seroquel is an “atypical” and ranks second. Like Abilify, it helps agitation, irritability, mania, and depression. It also helps sleep and may be better for anxiety.
It tends to cause daytime sedation but this usually goes away in 10-14 days. It may also cause dizziness upon standing. With long term use it can result in moderate weight gain. It is fairly short acting so it may need to be given twice a day and missed doses can be more problematic. Because many patients can’t tolerate higher doses it is probably not as good for depression as Abilify.
Overall it is effective, especially good for sleep and well tolerated. It is sometimes combined with Abilify.

3. LAMICTAL
Lamictal is an anticonvulsant and is my third ranked drug. It is especially good for Bipolar depression. Although it doesn’t help reduce manic symptoms, it does reduce manic episodes and was actually approved by the FDA for Bipolar maintenance. It is one of the most useful for rapid cycling (four or more episodes of depression or mania per year).

The only significant side effect concern is a rare serious rash that may require medical treatment. It only occurs in 1 per 1000 patients. To minimize any rash, the dose has to be very slowly increased, taking 6 weeks to reach the usual effective dose.
It is taken once a day in the morning. It has a very favorable side effect profile with no weight gain, sexual dysfunctioning, or sedation. I have many patients whose quality of life has been enhanced by Lamictal over the past few years.
It mainly treats depression and doesn’t help mania or agitation. It probably doesn’t help irritability and takes a few weeks to titrate. I rank it below Abilify and Seroquel.

4. LITHIUM CARBONATE
Lithium Carbonate is a salt that we all have in our system as a trace mineral. It was discovered in 1949 to help treat mania and to a lesser extent Bipolar depression. It effectively reduces episodes of both. It also reduces volatile temper outbursts and most strikingly reduces suicide risk by 800% by reducing impulsivity.
It is relatively inexpensive even in its more commonly prescribed longer acting forms, Eskalith 450 and Lithobid 300.
In spite of 35 years experience in the U.S. and 45 years in England it is much less prescribed in this country partly because there are no pharmaceutical companies really promoting it – there’s no money in it.
It has to be titrated carefully and occasionally blood levels are required. It tends to lower thyroid so thyroid levels have to be monitored more closely than usual.
Lithium does have some significant side effects, such as weight gain in many patients. Side effects like tremor, nausea, diarrhea, urinary frequency and excessive thirst can be managed by adjusting dose or other techniques.
It works for classic Bipolar I with manic episodes and depressed phases alternating with completely normal periods of time. It may work well as a stand alone medication. This is what Jane Pauley and the psychologist/author Kay Jamison take. I have patients who have done well on Lithium for literally decades.
There is an occasional patient that develops complications of kidney inflammation which can be a serious problem if its not stopped.
There is also a relatively low therapeutic index, meaning the difference between optimal dose and toxic dose is not very great. Blood levels can also be effected by extremes of diet and hydration. Because it competes with salt (sodium) in the body, high salt intake will decrease Lithium levels and it may lose its effect. No sodium intake (not eating) or high losses of sodium with extreme sweating, vomiting, or diarrhea, causes the person to save Lithium and possibly become toxic.
In spite of these side effect issues and potential risks there are more studies supporting its effectiveness in reducing major mood episodes than for any other medication. For someone frequently or chronically suicidal, or impulsive behavior, it appears to be more protective than anything else. I rank it as my 4th mood stabilizer.

5. ZYPREXA & 6. SYMBYAX
Zyprexa is an atypical that works very well for agitation, mania, depression, and sleep. It seems to work quickly. Symbyax is a combination of Zyprexa and Prozac. This combination is very effective for Bipolar depression. It is the only medication that has a formal FDA approval specifically for this diagnosis. I have had several patients whose depression was severe and a range of multiple antidepressants didn’t help. They had an excellent response to Symbyax.
I rank Symbyax (5th) above Zyprexa (6th) because of the frequent dramatic benefit for this group of desperately depressed patients. Unfortunately, the majority of patients on this medication gain a tremendous amount of weight, may have increases in cholesterol, triglycerides and adult onset Diabetes. I had one lady that gained 100 pounds in one year on Zyprexa. Thinner patients gain more than patients who are already obese-but thinner patients object to weight gain even more. With the exception of patients with anorexia nervosa, weight gain is a serious side effect. Another problem is cost. All of the “atypicals” are expensive, but these two are almost twice as much as the others.
Because Zyprexa takes 5 hours to reach maximum blood level, it is best taken around 6pm to induce sleep at normal bedtime, and then be worn off enough in the am-although morning grogginess is sometimes a problem.
In spite of the side effects (especially weight gain) I still use this medication in some patients but will usually shift to Abilify or Lamictal after they are stabilized.
One additional issue is that smoking may decrease blood levels of Zyprexa by 30%, requiring an increased dose and therefore an increase in price. Since almost all Schizophrenics smoke, this has major budget implications for government sponsored clinics, Medicaid, and insurance carriers-who of course pass on the cost.

7. RISPERDAL
Risperdal was the first “atypical” to be used in general clinical practice in the U.S. and therefore we have the most experience with it. It works well for agitation, mania, irritability, and also helps depression. It is not particularly good for sleep.
Risperdal comes in multiple sizes that are easily broken into 1/2 or 1/4’s, making for maximum flexibility of dose. This also helps with cost by buying the larger sizes.

Unfortunately, it has a lot of side effect issues-mostly in the long term. It causes moderate weight gain and frequently increases the hormone prolactin. This may cause breast enlargement (not popular with men), and sometimes lactation (not popular with men or women). There may be no obvious clinical effects of increased prolactin but since it lowers testosterone and estrogen it is frequently
associated with decreased libido. It may also increase risk of future osteoporosis in women. In addition, it is the most likely of the “atypicals” to cause movement disorders and has a risk of Tardive Dyskinesia. Taking it with Paxil or Prozac or being a genetically slow metabolizer may increase this risk by increasing blood levels. It is believed to be relatively safe in most people at doses less than 6mg per day. Because of its benefits and general tolerability, I rank it #7.

8. GEODON
Geodon is one of the newer “atypicals”. It is weight friendly and non-sedating and generally works for the full range of mood symptoms. Like Abilify, it may have more cognitive benefits. At lower doses it has antidepressant effects that predominate and this can be a problem, especially for manic or hypomanic patients.
It has to be pushed to higher doses to function well as a mood stabilizer and generally has to be taken twice daily. A big problem with it is that if you don’t take it with food the effect is cut in half. I haven’t seen many great responses.
It comes in capsules that are hard to titrate. It doesn’t help sleep (at least initially) and the food issue puts it further down on my list. It is effective and it is weight friendly. I rank it #8.

9. DEPAKOTE
I have twenty years of experience with this anticonvulsant type of mood stabilizer. Because of aggressive marketing and because using Lithium is more complicated, Depakote replaced Lithium as the top selling mood stabilizer. It was later replaced by the “atypicals” and Lamictal as most prescribed.
For a hospitalized acute manic Depakote has the advantage of being sedating and the full dose can be given on day one. But I can’t remember any patient saying, “Depakote is great.”
It causes weight gain, frequently daytime sluggishness and may cause hair loss (not popular). It also increases risk of polycystic ovaries in young girls which is a big problem.
Depakote does help mania and agitation. It also helps prevent migraine and it is still frequently prescribed. It can raise blood levels of many other medications by inhibiting metabolism and this can create confusion.
I don’t prescribe it much because the downside is as great as the benefits. I rank it 9th.

10. CARBATROL
Carbatrol is an anticonvulsant that has been used as a mood stabilizer since the late 70’s although formal FDA approval is still pending. It is used frequently by neurologists for seizure disorders, but use in psychiatry has been more limited, most especially because of its drug drug interactions.
It is a potent inducer of a liver enzyme (3A4) that metabolizes 2/3’s of all medications that we use. This means that it will lower levels of other medications so that doses of the other meds have to be adjusted. Lamictal doses, for example, have to be doubled if given with Carbatrol. Since Carbatrol also lowers estrogen and testosterone levels this can cause problems. The strength of birth control pills frequently has to be increased or unwanted pregnancies can result. Otherwise, it is fairly well tolerated and is especially useful in controlling symptoms of aggression. I rank it 10th.

11. CLOZARIL
Clozaril was the first “atypical” to be approved for schizophrenia. Because it can occasionally cause bone marrow suppression blood levels have to be done weekly initially and then every 2 weeks. It has other possible serious side effects such as seizures and other undesirable effects like drooling. It also causes substantial weight gain.
Because I knew I would never use it enough to really learn all its nuances I have never prescribed it even though it has been available for several years. The one patient I referred to the medical school to take it as a part of a study was accepted into the study. He then changed his mind. When I asked “how come?” he said, “they told me one of the side effects was death!” Hard to sell.
Having said all that, there are reports of patients with severe Bipolar disorder or Schizophrenia who do well with this drug and not on anything else. I rank it last.