Question: Are the terms “antipsychotic” and “mood stabilizers” the same?

– R.M.

Answer: There is no consensus about the definition of mood stabilizer – but at the least, it includes helping either mania or depression without worsening the other.

The term antipsychotic at this point means medications that block certain brain receptors (D2) that have been found to be overly active during classic psychosis including hallucinations and delusions. Abilify is one exception in that it doesn’t block D2 receptors but modulates them, i.e. decreasing activity when too high but increasing activity when too low. The term “antipsychotic” was reasonable with the older medications like Thorazine, Stelazine, Mellaril, and Haldol. They are not considered mood stabilizers because although they can help mania they can worsen depression.

The term “atypical antipsychotic” is misleading because these medications (Risperdal, Seroquel, Zyprexa, and Geodon) have many uses in addition to helping psychotic symptoms. They are used for treatment resistant depression and Obsessive Compulsive Disorder. They are also used for agitation, extreme anger and aggression. They may be helpful for addictions. Clozaril is different in that it has potential severe side effects that limit its use. Abilify is unique as previously discussed. These medications meet the standard of helping mania without worsening depression.

There is inadequate research to determine whether the “atypical” antipsychotics meet the stricter definition of mood stabilizer – help mania, help depression and help prevent future episodes of both – which means beyond 6 months after an episode. Seroquel has one good study for helping Bipolar depression. Abilify has evidence for preventing relapse up to 6 months. Zyprexa also has an indication for maintenance. At this time Lithium has the most supporting evidence as a mood stabilizer – but it’s been studied for 50+ years (on the U.S. market for 35 years).

Risperdal in the U.S. has FDA approval for mania and mixed episodes (mania and depression) but it doesn’t have controlled studies for Bipolar depression or maintenance. As I discussed in my article Ranking the Mood Stabilizers, my issues with Risperdal have to do with moderate risk for weight and metabolic problems and frequently elevation of the hormone prolactin. Since prolactin lowers hormones (estrogen and testosterone) it can cause decreased libido, increased risk of long term osteoporosis and possibly many other long term problems. Of course if it’s working well with no apparent side effects and other medications haven’t worked then on the basis of benefits vs. risks it makes sense to take it on a long term basis.

There are other options for treatment resistant depression. Making sure thyroid, estrogen and testosterone levels are good is important. Thirty minutes per day of vigorous physical activity and at least thirty minutes of bright outside light exposure are also important. Cognitive therapy can also be helpful. Sometimes adding a stimulant like Adderall, Concerta, or Provigil can be extremely helpful especially if there are problems with motivation, interest, and focus. Wellbutrin XL can be combined with an SSRI or Effexor or Cymbalta. Combining antidepressants or adding a stimulant have greater long term safety than most of the atypicals.

It’s important that you are getting adequate (7-8 hours) quality sleep(See sleep articles) but avoid excessive sleep because this can worsen depression. Of course all options need to be explored by your physician.

FAQs: Comparing Meds

In general, when we are aroused, vigilant, or alert and especially when in a “fight or flight” mode our appetite is suppressed.  The brain transmitters serotonin, norepinephrine, dopamine, and histamine decrease appetite, and being in a relaxed vegetative state increases appetite and low blood sugar causing carbohydrate craving. During physical activity appetite suppression occurs, but after activity hormones stimulate appetite to replace the energy  depleted energy sources.  When stress causes depletion of brain serotonin we eat to raise serotonin levels, or stress stimulates appetite by raising cortisol and insulin.  When we’re bored eating raises dopamine levels.

Inactivity as in hibernation causes excessive eating, and eating because of stress or boredom causes excessive intake of calories.  Eating sweets increases insulin, and insulin stimulates low blood sugar, carbohydrate craving and the roller coaster of high blood sugar and low blood sugar levels.  Intermittent acute stress leads to intermittent release of adrenaline, which causes the liver to dump sugar into the blood stream.  This high level of insulin then causes the low blood sugar cycle.  

Weighing the Risk Vs. Benefits of Medications that Affect Weight

Managing stress and eating the right foods is of preeminent importance in combatting the blood sugar cycling.  Further, some medications protect against these negative cycles, while helping you to lose or control your weight.  Many patients gain weight from certain medications, many of these patients feel a lot of guilt and shame because of their weight gain. Lack of self discipline and self indulgence can be a problem but for many patients it’s out of their control.  Some medications change brain functioning, and like a person with genetic obesity, they begin to save every extra calorie as extra fat.  Weight gained on medication sometimes comes off fairly easily with discontinuation of the medicine when no longer needed, but sometimes it seems the medication resets the weight-o-stat making it difficult to return back to previous weight.  

When using medications to lose weight, especially those that work by decreasing appetite or increasing control of eating, it is important to realize that stopping them could lead to gaining the weight back.  Frequently with a couple of extra pounds for good measure. In other words, there’s no medication that can be taken just to lose weight that effectively helps keep the weight off after it is discontinued.  Because of this,  it only makes sense to use medication  for  weight control if you need it for another condition, like stimulants for ADHD or thyroid medication for low thyroid. Sometimes long term use of pure appetite suppressants is useful just because the risks associated with obesity versus the relative long term safety of appetite suppressants is greater.

Fenfluramine (Pondimin) and d-fenfluramine (Redux) were used for 10 years in France and an additional 3-4 years in the U.S. before discovery that they caused serious complications, especially heart valve abnormalities and/or pulmonary hypertension, and especially when used in combination with phentermine. The reason for this is because Fenfluramine increases serotonin activity and Phentermine increases norepinephrine activity, both which can constrict arteries.  The combination fen-phen was never promoted by any pharmaceutical company but became popular after a paper was published by a doctor who had good success with this combination. After realizing the harmful effects of the combination, Fenfluramine was taken off the market, and since then many law suits have been filed.  Though there is no doubt that this combination can be dangerous, claims of damage most likely exceed actual damage. The lesson learned from phen-fen is the same as the one recently learned from Vioxx. Controlled studies of most medications are relatively short term. There is always some potential risk with the long term use of medications, so it is alway important to ask, “What are the Potential Benefits vs. the Potential Risks”?

Medications and Weight Control From the Worst to the Best

The following medications are commonly used in treating stress disorders.  I will list them starting with the worst for weight management (the one most likely to cause weight gain) and end with the best medication for weight management. 

Zyprexa

Clozaril

Symbyax

Remeron

Seroquel

Risperdal

Lithium

Depakote

Neurontin

Anafranil

SSRI’s

Abilify

Geodon 

Clozaril, Zyprexa & Symbyax: Symbyax is a combination of Prozac and Zyprexa, and these three are tied for the most likely to cause weight gain. They block the serotonin receptor associated with satiety. In addition they block histamine, some dopamine, and increase the hormone prolactin.  Both medications are considered a high risk for causing metabolic syndrome, and patients taking these medications should have blood work done regularly to check their lipids and glucose. 

Remeron:  This antidepressant blocks histamine and the satiety receptor, but because it also increases serotonin and norepinephrine, it is not as bad as Zyprexa and Clozaril.

Seroquel:  This atypical medication poses moderate risk for metabolic syndrome and sometimes causes substantial weight gain, because it acts strongest as an antihistamine.

Risperdal: This medication also poses moderate risk for metabolic syndrome. The moderate risk for weight gain may be related to the fact that it has a strong blocking effect on dopamine and is the most likely of the newer medications to increase the hormone prolactin which may contribute to increased appetite.

Lithium and Depakote:  These medications are generally used to treat Bipolar disorder and they pose a moderate risk for increased weight over the long haul.

Neurontin and Anafranil: Neurontin and the tricylic antidepressant Anafranil (Clomipramine) can also lead to significant weight gain over time.

SSRI’s: The most commonly prescribed medications for depression and also commonly used for anxiety are the group referred to as SSRI’s (selective serotonin reuptake inhibitors). These include Prozac, Zoloft, Paxil, Lexapro, and Celexa and low doses of Effexor. The first one (Prozac) has been available since 1987.  Again, to quote Einstein, “keep it as simple as possible, not simpler”. The effect of SSRI’s on weight is complicated because there are 3 different phases in the mechanism of action.  To simplify this process, here is a breakdown of the phases:

    Phase 1  By blocking the reuptake of serotonin into the sending cells, Serotonin builds up in the synapses and stimulates multiple receptors on adjacent cells.  This happens within 24 hours and goes on for several days.
This immediate boost in serotonin can help premature ejaculation, decrease carbo craving and can help premenstrual dysphoric disorder. It can also destabilize bipolar disorder.

    Phase 2  After one week on Effexor, 10 days on Lexapro, 2 weeks on Celexa, Prozac and Paxil or 3 weeks on Zoloft, the effects of the increase in serotonin begin to modulate activity within adjacent cells and will begin to change receptor activity on the sending cells also.  These modulating effects help clinical anxiety and depression.

    Phase 3  The least well understood phase of SSRI activity occurs after several weeks.  Because most controlled studies of SSRI’s only last 6-8 weeks, the information on how they work long-term is limited.  However, the proof that changes continue to take place can be explained when used to treat Obsessive Compulsive Disorder, because it usually takes 12 weeks to see positive changes.  The down regulation of serotonin activity in the brain presumably causes the change, because when serotonin levels increase a messages goes from the brain to the cells and says “we have enough, you can decrease production”.

This mechanism may explain how SSRI’s help anxiety and panic disorder by decreasing serotonin release  where there is hypersensitivity to serotonin.  A common phenomenon seen in patients on SSRI’s has been referred to as “poop out”.  It is not clear whether this is due to excessive down regulation of serotonin release or if it is due to the fact that serotonin causes a decreased release of dopamine  which is the drive and motivation system.  Symptoms of “poop out” include feeling “blah”, blunting of normal emotions, sexual dysfunction and weight gain that can occur due to decreased serotonin activity and/or decreased dopamine release.  Because the weight gain doesn’t occur until several weeks or months of being on an SSRI most doctors and patients don’t see the cause and effect relationship.  In some cases, it may be correctible by decreasing the dose.  Unfortunately more often the “blahs” are seen as a return of the depression so the dose is raised, which temporarily helps by raising serotonin but eventually down regulates serotonin even lower.  Sometimes lowering the dose or stopping the SSRI causes return of severe anxiety, OCD, or depression. Adding Wellbutrin XL or a stimulant may help.  Finding a different medication that is as effective for anxiety and depression that does not cause weight gain is difficult, sometimes impossible.

Of the SSRI’s Paxil seems to be the most likely to cause weight gain but any of them can be a problem in the long term.  Effexor XR is mainly an SSRI at 37.5-75mg but does have some norepinephrine effect even at the lower doses, which may help protect against the “poop out” syndrome.  Doses of more that 150mg of Effexor XR and Cymbalta are not as likely to cause long term weight gain presumably because of the combined serotonin and norepinephrine modulation, but weight gain does occur in some patients over the long term.

Abilify and Geodon: These atypicals have the least likelihood of causing metabolic syndrome and tend to be weight neutral. Thin people may gain a little weight on these meds long term, but overall they don’t pose a huge risk of weight gain.

Hormones – Some women gain weight on the hormones estrogen and or progesterone. Estrogen, especially estradiol, may be a particular problem if taken orally.

There are several meds or groups of meds that are essentially weight neutral:

 Meds that can help with weight control:

I have been prescribing medication for stress disorders since 1966, and over the long term, the medications that have been the most helpful in controlling weight are the amphetamines prescribed for ADHD.  Although, when short acting forms of the stimulants are taken they sometimes cause rebound overeating in the evening and this can also occur on days when not taken.  Despite popular belief, the efficacy of stimulants on weight loss is not due to appetite suppression, although appetite suppression occurs when initially starting some stimulants, especially in kids and teens, but I believe it mainly increases control and decreases impulsivity.  This prevents eating out of stress or boredom. I have the most experience and success with Adderall XR, the long acting form, since tablets, the short acting form, are more likely to cause rebound.  Dexedrine and Desoxyn also work, most likely by setting the “weight-o-stat” lower.  The methylphenidate type stimulants are usually not as effective for controlling weight, and the longer acting Concerta (soon to be available), Focalin XR, Ritalin LA, and Metadate CD are better than short acting meds.  Stimulant often increase energy and motivation, which may be another attribute associated with their weight loss efficacy.

ADHD and Weight Issues

ADHD increases an individuals risk of abusing alcohol or drugs because part of the physiology of ADHD is the need for more stimulation than the non-ADHD person. There are several different polymorphic genes more commonly seen in ADHD and nearly all result in low dopamine activity in the brain, specifically the nucleus accumbens.  Every addictive substance or activity increases dopamine, and food is one of the strongest enhancers of dopamine.  For this reason, being ADHD may result in overeating and excess body weight. In one study using Adderall XR in people who were ADHD and obese, they found the obese individuals lost a significant amount of weight. In contrast, people who were ADHD but within normal weight range did not lose a significant amount of weight.

Summary

All of this is not say you need medication to control your weight. But if all of your efforts to maintain not only healthy weight but fitness have failed, you may consider trying medication. When contemplating the use of medication the question is always, “what are the potential benefits vs. what are the potential risks”? Nietzche said “first be a good animal”.  You can’t be mentally healthy if you’re not physically healthy. Two thirds of the U.S. population are overweight.  Being overweight, especially abdominally, increases risk for cardiovascular disease, diabetes, stroke and other health problems, and it’s not so good for self-esteem either.  I believe the main reason weight has become a rising epidemic exists because  we weren’t made for this world.  The world of hunting and gathering that we adapted to was a much more active lifestyle.  Food was not always plentiful, and additives and refined foods did not exist.  People were at the mercy of ice ages, droughts and Mother Nature and our brain conspires to protect us from food shortage by storing energy as fat.  Unfortunately in today’s world, genetics (polymorphism) and behavior (brain plasticity) conspire to make us overweight.  There are behaviors to help you lose and behaviors that make you gain, including ironically, dieting just like there are medications that make it hard not to gain weight and medications that make it easier to lose weight.  It’s more important to be physically fit than to be within the ideal range of body fat, which is where in realizing your full potential you have to “first be a good animal”.

Click here to see how Dr. Jones determines “Best Meds”
I decided to discuss anxiety and depression together because they usually occur
together, have a lot of the same genetic predisposition, and respond to a lot of the same medications.
Anxiety is like spending more money than you make – depression is like being in debt. In anxiety there is excessive activity in certain brain modulators, especially serotonin and norepinephrine. There also may not be enough GABA, the brain’s natural tranquilizing system.
Anxiety symptoms (and ultimately clinical depression) are caused by stress overload and more importantly stress vulnerability (genetics and early life experience). Unfortunately, the worse your genetics the more likely you are to have early life trauma, loss, abuse, i.e. “double jeopardy”.
There are five types of anxiety disorders – mostly treated with the same medications, but each responding to different types of cognitive behavioral therapy.
They are:
• Generalized Anxiety Disorder
• Panic Disorder +/- Agoraphobia
• Social Anxiety Disorder
• Obsessive Compulsive Disorder
• Post Traumatic Stress Disorder
Treatment Options

When treating anxiety disorders, I usually start with a benzodiazepine or something that works quickly. In some cases, like panic disorder and occasionally social anxiety or GAD, this along with cognitive behavioral therapy is all that is needed. But usually for OCD and PTSD and frequently for the other anxiety disorders, an SSRI or SNRI is the more definitive treatment. The problem is they take 2-4 weeks or more to help, and in the meantime, their side-effects make things worse. So, usually I start with a benzodiazepine and add on an SSRI plus cognitive behavioral therapy. Then, as the patient gets back to normal, frequently we can taper one of the medications. Benzodiazepines, not SSRI’s, can also be taken on an as needed basis.
Generalized Anxiety Disorder combines excessive worry with hyperarousal. It responds to benzodiazepines, SSRI’s, SNRI’s, Tricyclics, some anticonvulsants (Neurontin, Gabatril), and Buspar.
Social Anxiety Disorder – the generalized type responds to SSRI’s, SNRI’s, benzodiazepines, some anticonvulsants, MAOI’s and sometimes stimulants.
For specific performance anxiety, we often use beta blockers +/- alpha blockers to prevent heart pounding, shaky voice or hands, blushing or excessive sweating. These meds are most often used situationally.
Panic Disorder – Benzodiazepines, especially Alprazolam and Clonazepam, SSRI’s, SNRI’s
Obsessive Compulsive Disorder – SSRI’s, Anafranil, Clonazepam, Atypicals
Post Traumatic Stress Disorder – SSRI’s, SNRI’s, benzodiazepines, Atypicals, sometimes Beta Blocker’s (especially the first 24 hours)
PTSD is much more than anxiety disorder and will be discussed in detail in a future article.
In clinically depressed states, there are one or more deficits in brain modulators serotonin, norepinephrine, and dopamine. Stress hormones, especially cortisol and cortisol releasing factor, are elevated. Stress hormones are bad for your physical and mental health. Modulating brain transmitters with antidepressants normalizes stress hormones and therefore protects your health.
The most prescribed antidepressants are SSRI’s and SNRI’s and Wellbutrin. If a benzodiazepine is needed for anxiety Alprazolam is preferable. Other medications, like stimulants, hormones, sleep medications, and mood stabilizers, may be used, and MAOI’s are still occasionally used.
When treating depression I start with sleep problems and anxiety, if present. Antidepressants take time to work, and people who are suffering with clinical depression need some reason to be hopeful – the sooner the better. For recurring depression “the dose that got you well keeps you well”. So, we need to choose carefully, minimizing long term side-effects.
Benzodiazepines (Bnz)
Benzodiazepines have been used since 1960. They all work by enhancing GABA, the natural tranquilizer in the brain. We have more GABA than any other neurotransmitter. Some people with anxiety disorders have been found to have a deficiency of GABA in areas of the brain that regulate emotion. Because benzo’s work indirectly, they are relatively safe (i.e., you won’t die from an accidental or intentional overdose because they don’t suppress breathing like barbiturates and alcohol do in overdose amounts).
One myth that complicates the use of BNZ by doctors and patients is that they are “highly addictive”. The fact is that if they are taken regularly, so that they are always in your system, over time you develop a physical dependence. This means that you have physiologically adapted to the medication, and if you stop it suddenly or go off it too fast you can have withdrawal symptoms. But, physical dependence has nothing to do with addiction. Addiction is compulsive behavior in spite of negative consequences. Most people take medication to feel more normal and to be able to function. Addicts aren’t interested in feeling normal. It’s either “too boring” or “too stressful” or both. They prefer to be “high” or “numb”. The small percent of patients who abuse bnz’s are usually wanting to be numb. But this is less than 5% of patients who are prescribed one of these medications. Pain meds, especially hydrocodone types, are 3x more likely to be abused.
All bnz’s multiply the effects of alcohol, and mixing them will significantly increase the effect of both. This is especially a problem with driving – if mixing alcohol and bnz’s don’t drive. This is especially a problem with longer acting benzo’s.
Best Benzodiazepines
Xanax (Alprazolam) has been available since 1980 and is my first choice. I have many patients who have taken this medication either regularly or as needed for up to 25 years. Literally hundreds of patients I have treated with Xanax will say things like “it saved my life”. It is especially good for panic attacks and anxiety and it may help depression (although it’s not an antidepressant). There are cases where it has caused hypomania in a Bipolar patient. It has very few side effects – mainly sedation if too high a dose. The regular tabs are short-acting (4-8 hours), and most people who take them for a continuous effect take 4 doses per day. There is now an XR form that can be taken once or twice daily. Xanax (Alprazolam) was the most prescribed medication in 2003 for stress disorders in the U.S.
Niravam (Alprazolam orally disintegrating tablet) is now available. It is a rapidly dissolving wafer. Many patients report that it is convenient and faster to take. Some patients prefer to dissolve it under the tongue. Wafer forms of medication are especially helpful with panic patients who frequently have difficulty swallowing pills. They usually have more confidence when they have a medication with them that doesn’t require water and can be taken inconspicuously.

Klonopin (Clonazepam) is a close 2nd to Xanax. It is now available as Klonopin wafers that dissolve immediately, and used sublingually (under the tongue), seem to work faster. This is especially useful for panic attacks and acute anxiety. Klonopin is good for racing thoughts (helps with mania) and obsessing (is often added for OCD) and social anxiety. It is not as good for general anxiety. It is twice as strong as Xanax for panic attacks so 1mg Xanax = .5mg Klonopin. Klonopin lasts for 6-12 hours. It has more potential side-effects, probably because it seems to be the only bnz to decrease release of serotonin. It can worsen depression especially at doses above 2mg/day, and it can cause significant sexual dysfunction. It’s because of the potential side-effects of Klonopin and the greater benefit in general for anxiety and depression that I rank Xanax 1st and Klonopin 2nd.
Ativan (lorazepam) is relatively short acting like Xanax and is only 1/2 as strong for panic (1mg Xanax = 2mg Ativan). It is relatively effective for anxiety and is also a good muscle relaxant. It is one of the milder medications in this class. Abuse potential is similar to Xanax. It doesn’t go through normal liver metabolism, so it is safer in patients with liver problems.
Tranxene (clorazepate) and longer acting Tranxene 50 are long acting and mild. They have a relatively low abuse potential and can be taken once daily. They provide help with anxiety for 24 hours. They are not helpful for panic disorder because it would require very high doses.
Valium (diazepam) has been around for over 40 years. Of the bnz’s it is the most likely to be abused because it is highly fat soluble and has the quickest onset of action that might provide a euphoric feeling. It is also long acting, so that it may take 2-3 days or longer to be completely out of the system. It is good for anxiety and muscle relaxation, but not panic attacks. I have a few patients that have been on it for years and do well on it, but I very seldom put new patients on it.
Serax (oxazepam) is not used much anymore. The main reason that it use to be prescribed is that it is the least likely to lead to disinhibition, anger, and aggression in impulsive type people. I use it very seldom now. Like Ativan, it doesn’t go through normal liver metabolism.

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More on antidepressants
Read Dr. Jones’ response to email on benzo’s

See introduction
ANTIDEPRESSANTS
SSRI’s, or Selective Serotonin Reuptake Inhibitors, modulate the serotonin system. They keep serotonin in the synapses between cells longer, which increases serotonin activity. This happens within 12 hours and some conditions like Premenstrual Dysphoric Disorder and premature ejaculation respond very quickly to these medications. It takes 2-3 weeks for SSRI’s to start helping anxiety and depression. This is because it’s not the direct effect of serotonin but how it effects the receiving cells and the sending cells. I call SSRI’s modulators because they increase serotonin activity if it’s too low (as in depression) and decrease it if it’s too high (as in anxiety). Sometimes serotonin is high in some brain areas and low in others.
SSRI’s started with Prozac in 1987 and now include Zoloft, Paxil, Luvox, Celexa, and Lexapro. I include Effexor XR 37.5 to 75mg in this group because at these doses its primary effect is on serotonin. At higher doses (150-225mg) it is an SNRI. SSRI’s, including low doses of Effexor XR are better for anxiety disorders than depression. All SSRI’s have potential side-effect issues in the short term and long term.
The biggest problem with the SSRI’s is in the long term. This is what matters the most to patients because they usually need these medications long term. Over several weeks to months there is frequently a “poop out” effect associated with some decrease in energy/motivation. Sexual dysfunction, especially loss of libido, and weight gain are common. Sometimes these can be improved by lowering the dose or adding another medication (like Wellbutrin XL), or in the case of Effexor XR, either increasing or decreasing the dose. But sometimes patients prefer to stop the medication or change to something else.
Protein binding is an important factor with the SSRI’s because it’s only the percentage of the medication that is free (not protein bound) that interacts with the receptors on the cells. Medications are like keys, and receptors are like locks. Medication can either turn on the receptors or plug them up and prevent them from being turned on.
BEST SSRI’s

1. EFFEXOR XR
Effexor XR is my first choice for an SSRI mainly because it is the one that in my experience patients are most likely to be happy with long term. It is the quickest to work probably because it has the lowest protein binding (27%). I expect some benefit for anxiety/depression by 7 days. Effexor XR doesn’t have any significant drug-drug interactions. It has the flexibility of being increased to higher doses if/when needed, so that it becomes also a norepinephrine reuptake inhibitor. (see SNRI’s below) Effexor XR comes in capsules that can be opened and sprinkled on food to take partial doses or for people who have trouble swallowing.
Of the SSRI’s it is one of the least likely to have drug-drug interactions. It is well tolerated. Occasionally it causes initial jitteriness or nausea, but these side effects go away quickly. In general, long term side effects are the lowest of this group, except for delayed orgasm – sometimes a benefit for men. If it occurs in women, taking it after sex sometimes solves the problem.
Because Effexor XR clears the system in 3 days, it can cause rebound symptoms if stopped abruptly. It needs to be gradually tapered. On the other hand, for women who may get pregnant unexpectedly they can stop taking it and have it out of the system before maternal blood mixes with the embryo. Also, when used for Premenstrual Dysphoric Disorder, it is out of the system more quickly once stopped. With this type of very short term use, there are no rebound concerns.
2. LEXAPRO
Lexapro is my 2nd choice in this category. It has the most pure effect on serotonin, and this is an advantage for patients who don’t tolerate any norepinephrine effect. (see SNRI’s below) Because it is 56% protein bound, it is fairly rapid in onset of benefit – I expect improvement beginning in 10 days.
It has flexible dosing since it comes in tablets that can be cut. Like Effexor XR, it has minimal drug-drug interactions. Rebound is not a significant issue at least in adults.
CELEXAis 1/2 Lexapro and 1/2 relatively inactive. It acts much in the same way as Lexapro.
PROZAC
Prozac (fluoxetine) is my 3rd choice because of my long term success with many patients, especially with Obsessive Compulsive Disorder. It may be the safest in kids and young teenagers, probably because it has such a long duration of action. It takes 6 weeks to clear the body, and therefore, rebound symptoms are not an issue. Weight gain and sexual dysfunction aren’t as bad as with some of the other SSRI’s. It has 96% protein binding so onset of action usually takes at least 2 weeks.
A major problem with Prozac is that it blocks a certain enzyme system that will increase other medications. These include tricyclics, Risperdal, Dextromorphan, Strattera, and others, and decreased benefit of pain medications.

PAXIL CR
Paxil CR is a controlled release form of Paxil. 25mg of CR is equal to 20mg of the regular Paxil. It is the only SSRI that has a formal approval for all five anxiety disorders. It may be the most effective SSRI for Social Anxiety Disorder possibly because it has blocking action on the parasympathetic nervous system – which is frequently overactive with social anxiety. This blocking effect may also contribute to a sedative effect that it sometimes has – which may help with sleep even when first starting it. But the blocking effect may also contribute to side effects like constipation and sexual dysfunction.
In my experience Paxil has the worst rebound symptoms if stopped suddenly or doses are missed. It may also be more likely to cause agitation in kids and young teens. It is probably the worst SSRI for weight gain and sexual dysfunction. It also is the strongest blocker of one of the liver enzyme systems – blocking benefit from pain pills related to codeine or hydrocodone and also increasing levels of other meds like TCA’s, Strattera, Risperdal, and others. This can potentially cause toxic levels of these other meds. Because of the side effects and drug-drug interactions, I only prescribe it when other medications have not worked well. I do have many patients who have done well on it especially for Social Anxiety Disorder.
ZOLOFT
Zoloft was the 2nd SSRI available, so I had a lot of experience with it early on. It was also one of the first to be formally approved for many of the anxiety disorders. It has some effects on dopamine, and one study showed that at doses of 150mg, it had comparable benefits to Effexor. Unfortunately the dopamine effect may cause anxiety or restlessness that is sometimes severe. One 10 year old girl I had on it described her side effects as there was something inside of her that she wanted cut out because she couldn’t stand it (severe inner restlessness). It is the least likely to cause drowsiness or sluggishness and drug-drug interactions are mild (except at higher doses).
Mainly, I rank it low because over the years in my experience the percent of people who do real well on it long term is very low.
LUVOX
Luvox is now only in generic and is only formally approved for OCD but is not necessarily better for OCD than any other SSRI (several are also formally approved for OCD). I have a couple of patients on it – mostly because they were on it when I first saw them, and it seems to work o.k. So “if it ain’t broke, don’t fix it”.
The reason I rank it last is that it has a lot of side effects and the most drug-drug interactions. It’s the most likely to cause drowsiness and the most likely to cause insomnia. It prolongs the effect of caffeine by several hours, which may also contribute to a feeling of anxiousness. For these reasons I rank it last.
One indication may be for people who take Zyprexa – especially if they smoke. Luvox will decrease their daily dose requirement – which could save several hundred dollars per month. How esoteric is that?
SNRI’s
Serotonin Norepinephrine Reuptake Inhibitors are serotonin modulators (SSRI’s), and norephinephrine modulators (NRI’s).
By blocking the reuptake of norepinephrine SNRI’s modulate this system just as SSRI’s modulate serotonin. Adding the norepinephrine effect increases benefit for generalized anxiety and especially increases the benefit for depression. In multiple studies antidepressants that modulate both serotonin and norepinephrine consistently help more patients reach full remission.
Chronic major depression is associated with low serotonin and low norepinephrine levels and this results not only in increased pain from all causes, but multiple other physical/medical problems such as urinary and sexual dysfunction.
It also seems that the norepinephrine effect reduces “poop out” seen so frequently with SSRI’s. It may also help with ADHD.
1. EFFEXOR XR 150-225mg
I rank Effexor XR as my #1 choice in this category. As the dose of Effexor XR goes up, the effect on serotonin levels off and the effect on norepinephrine increases. Effexor XR has the flexibility of being an SSRI at lower doses and an SNRI at higher doses. It works quicker (probably due to low protein binding), has no significant drug-drug interactions, and has a proven record for the full range of anxiety disorders and depression. In my experience over the long haul, it has the greatest benefit and the best tolerability of any antidepressant, and I therefore rank it my #1 antidepressant.
2. CYMBALTA
I rank Cymbalta as my #2 choice in this category, partly because it has been on the market for less than a year, so we don’t have a lot of experience with it. It works well for depression, and it may help all the anxiety disorders. But the studies haven’t been done. It may not be tolerated by panic patients. There are more controlled studies with Cymbalta showing benefit for all kinds of pain than any other antidepressant. It is especially helpful for back pain.
Some patients don’t tolerate it very well, and the dosing isn’t as flexible because it’s in capsules that can’t be sprinkled. There are issues with drug-drug interactions – it shouldn’t be mixed with Paxil or Prozac. It will weaken the effect of pain medications. 7% of Caucasians are genetically slow metabolizers and may have a significant increase in blood levels of Cymbalta and may show more side effects. Cymbalta will increase Strattera, Risperdal, Dextromorphan, and others. Having drug-drug interactions increases the complexity of prescribing any medication.
Because of its proven track record, I start with Effexor. But for those that don’t do well on Effexor for whatever reason, I have had some success with Cymbalta, especially for depression associated with chronic pain.

Other Antidepressants
WELLBUTRIN XL
Wellbutrin XL is a totally different type of antidepressant. It is not a reuptake inhibitor, so it is not a modulator like the SSRI’s and SNRI’s. Its mechanism of action is not as well understood but we know it increases norepinephrine and to a lesser degree increases dopamine. Wellbutrin’s main benefit is to increase motivation, energy and interest and to restore the capacity for pleasure and enjoyment that is often lost when someone is clinically depressed.
Sexual dysfunction, (reduced libido, arousal, orgasmic delay or absence) can be a part of clinical depression or a side effect of SSRI’s or SNRI’s. Wellbutrin frequently improves sexual functioning either given alone or with other antidepressants.
Wellbutrin may help some of the symptoms of ADHD, but like Provigil, Tenex, or Strattera it doesn’t have the level of effectiveness that the stimulants (Adderall XR, Concerta, etc.) have.
Wellbutrin is the most effective medicine currently on the U.S. market to decrease craving for smoking and to make it easier to quit or at least cut back. It was marketed for smoking cessation under a different name, Zyban, which I thought was silly and causes a lot of confusion.
The best thing about Wellbutrin is that it doesn’t cause weight gain or sexual dysfunction short term or long term. It may cause nervousness, irritability, insomnia or constipation.
Wellbutrin is not a broad spectrum antidepressant like Effexor XR or Cymbalta. It is not useful for premenstrual dysphoric disorder, anxiety disorders or the cognitive symptoms of depression. It is not as good for sadness and guilt. But overall it is probably the best tolerated antidepressant long term, and many of my patients take it.
The XL form is better tolerated than the SR (now in generic) and especially better than the short acting tablets which are much more likely to cause side effects and lower seizure threshold. Caution still is necessary even with the XL in someone with an elevated risk of seizure either because of a previous seizure or severe head injury. It is also not safe in actively purging bulimics. In over 15 years of using Wellbutrin, the only seizures I have seen have been associated with abruptly stopping Xanax – usually with excess levels of shorter acting Wellbutrin. For most patients it is a non-issue.
Wellbutrin XL is very good for motivation, interest, and pleasure, but because it doesn’t do well with the whole range of depressive symptoms nor with anxiety disorders, I rank it 2nd overall of the antidepressants.

REMERON
Now available in Sol tabs that dissolve immediately for those who have trouble swallowing like the elderly and young children. The regular tabs are now available in generic.
Remeron is a broad spectrum antidepressant that is sometimes used to immediately enhance sleep and appetite. I tell patients you’ll sleep the first night and you’ll gain weight in your sleep. For people who have lost a lot of weight due to depression or for the elderly who have no appetite with or without depression this is very helpful. It is also sometimes used to treat stimulant side effects – especially in preadolescent boys who are usually not interested in losing any weight.
I use Remeron most often to enhance other antidepressants, especially Effexor XR. In addition to helping with sleep and appetite, it accelerates the antidepressant effect of Effexor XR and blocks side effects so that I can push the dose of Effexor rapidly – this is especially important with severe melancholic depression.
I usually start at 7.5mg or less because a.m. sedation/grogginess is so common. Starting with a higher dose may be less likely to cause a.m. sedation but may actually be worse, so I prefer to start low. This effect improves in a few days.
Remeron is usually not a good long term treatment because of the carbohydrate craving and weight gain. One lady told me, “Doctor you don’t understand. I got up during the night, drove to an all night grocery store and bought a cake. Then I went home and ate the whole cake.”
Because of daytime drowsiness that is so common and major league weight gain my overall ranking for Remeron is low. But for certain situations or for short term use it is very effective, and it’s in generic so reasonably priced.

Mood stabilizers are the most powerful and most important medications that physicians/psychiatrists have to treat the most severe stress disorders, including bipolar disorder, schizophrenia, agitation and/or psychosis associated with many disorders, even Alzheimer’s and other dementias. They are the most effective treatment for all forms of excess anger/aggression. More recently, we have learned that they are effective in highly recurrent clinical depression or depression that doesn’t fully respond to antidepressants. They include all the "atypicals," some anticonvulsants and Lithium. They can be used alone or added to other meds. Atypicals are sometimes added to an SSRI for treatment resistant OCD.
The goal in treating any stress disorder is complete resolution of all symptoms allowing for optimal functioning and quality of life. We first maximize any particular medication – best dose, best time(s) of day. If not helping significantly or not well tolerated, we stop it. After maximizing the benefit of a particular med, if we still have significant symptoms remaining, we will carefully add another med.
In bipolar disorder, multiple meds are the rule not the exception. In one study, less than 20% of bipolar patients needed only 1 med and 35% needed 4 or more.

All of these medical treatments are in the context of counseling about important aspects of lifestyle, especially sleep, physical activity, and general health habits. Addiction counseling or psychotherapy is often but not always needed.
The average person with a stress disorder has an average of 3 different conditions, each of which needs to be considered. Since there’s so much overlap, sometimes we can choose one medication that treats 2 or 3 concurrent conditions. Implicit in all this is that a complete evaluation needs to be done before a decision can be made for what treatment is most likely to work best.
Unfortunately, at our current stage of neuroscience, there is no way to determine with certainty which treatment will be best in any individual. Soon, we will be able to make better choices because we will be able to look at each person’s genetic profile and do brain imaging to show which areas are over or under active. We will also have many new treatment options.
For now, we combine the best current science with the art of medicine to make the best educated guesses. We will use trial and error. We will always start with a complete evaluation and also monitor outcome in a comprehensive manner. If what we are doing isn’t working, we will do something else. We will think systematically, but also listen to our intuition, which is smarter than we are. We will work as a team, and we will not settle for less than the optimal quality of life.

HORMONE TREATMENTS FOR MOOD DISORDERS
Strictly speaking, hormones (especially thyroid and estrogen) are not mood stabilizers, but, in my experience, need to be addressed first in all mood disorders.
THYROID
The thyroid hormone T4 (Synthroid) helps to stabilize mood, but needs to be in the upper 1/4th of the normal range. Another thyroid hormone, T3 (Cytomel), acts more like an antidepressant. Thyrolar and Armour thyroid provide T4 + T3.
TESTOSTERONE
In men with depression and low testosterone – supplemental replacement hormone has anti-depressant effects. Unfortunately, oral testosterone is not effective in men. Injections are a hassle. Patches and gels are expensive and frequently not covered by insurance.
DHEA
A recent study found that supplemental DHEA, which is an inexpensive over-the-counter, may help depression. It is a normal hormone that slowly declines in both men and women. It turns into partly estrogen, partly testosterone.
ESTROGEN & PROGESTRONE
I have treated many women over the years that were perimenopausal or menopausal in whom I was not able to control their depression or mood swings without supplemental estrogen. There is confusion and controversy regarding the use of hormone replacement therapy (HRT) in menopausal women. Each study seems to contradict the one before.
The confusion is due to multiple factors – usually not addressed in the studies. The simplest factor is dosage – lower doses are probably effective and don’t have significant risk issues. Menopausal women who still have their uterus have to take progesterone if they take estrogen. Progesterone takes away from the estrogen benefits in the brain (mood, memory, verbal, fluency). It also makes a difference what kind of progesterone is taken – synthetics (Provera and others) or natural (prometrium and others). More important is how progesterone is provided. Intra-uterine or intra-vaginal probably does not interfere with brain benefits of estrogen.
Another factor is what type of estrogen and how it’s taken. Conjugated estrogens (Premarin and Cenestin), containing many of the different types of estrogen, can probably be taken by mouth without causing possible reductions of many hormones.
Taking Estradiol (the most active form of estrogen) by mouth (Estrace, Estradiol, most birth control pills) causes the liver to make more binding proteins for thyroid, testosterone and the Estradiol itself. This reduces the effect of each of these unless the woman compensates by making a lot more of this hormone. Each woman is different, but I have seen many patients where the oral Estradiol causes low effective hormone levels.
Then there are the studies that scare women away from HRT. These studies usually focus on a small subgroup of women and aren’t relevant to the average woman.

Click here to see how Dr. Jones determines “Best Meds”
In my clinical experience mood disorders are the most challenging and in many ways the most difficult to treat. Frequently mood problems lead to substance abuse, which makes them worse. Lifetime suicide risk for Bipolar Disorder is 15%. Only 1% of the population has classic Bipolar I disorder (the old term – manic depressive.) Frequently, they’re psychotic; usually, they require hospitalization.

Much more common is what is now being called Bipolar spectrum disorders. This includes lesser degrees of mania and episodic rage attacks. Antidepressants tend to aggravate Bipolar symptoms, or at least increase the frequency of abnormal mood cycles. Bipolar disorder means that in addition to symptoms of depression, there are symptoms of mania or hypomania (see newsletter on Bipolar Disorder).

Mood stabilizers by definition ideally help depression and/or manic symptoms – but at least help one without making the other worse.  Antidepressants and stimulants aren’t mood stabilizers because they usually aggravate manic symptoms.  Klonopin and the old-fashioned antipsychotics like Haldol and Navane don’t count because they can aggravate depression.

The 1st mood stabilizer available in the U.S. was Lithium Carbonate in 1970.  In the late 70’s, Tegretol (now Carbatrol), an anticonvulsant, was added.  In the early 80’s, Depakote was found to help especially manic symptoms.  Then in the 90’s, we started getting the 2nd generation antipsychotics, “Atypicals”: first Clozaril, then Risperdal, Seroquel, Zyprexa and Geodon, and most recently, the 1st of the 3rd generation, Abilify.  Also in the 90’s we found that an anticonvulsant, Lamictal was especially good for Bipolar Depression.  It reduces manic episodes.  It is not useful in treating acute mania.
What makes these medications so important is that it is estimated that 1/3 of clinical depression is really part of a Biploar Spectrum.  This means 8% of the population could be effected.  Many alcoholics and drug abusers are self-treating a bipolar mood disorder.
Most recently, highly recurrent unipolar depression (NO manic symptoms) may respond better to mood stabilizers than antidepressants, especially if early onset (20’s or younger) plus family history of Bipolar Disorder, frequent or severe episodes, history of less than optimal response or poor tolerance to antidepressants or stimulants.

My ranking of these medications is based on my clinical experience plus my knowledge of the research as well as experience of experts in the field.  The factors I considered were: the range of symptoms treated, the degree of benefit for these symptoms, and relative lack of side-effects, especially in the long term.

To maintain stable mood, before considering formal mood stabilizers address life-style factors:

1. Sleep (ideally 7 hours normal sleep every night) is the single most important.
2. Regular aerobic activity – 30 minutes daily preferable.
3. Maintain good levels of estrogen/testosterone.
4. Keep thyroid level in the high average range.

Hormone Treatments for Mood Disorders

There are 3 categories of mood stabilizers. (The majority of bipolar patients require more than one medication).
They are:

All Atypicals:
Abilify
Seroquel
Symbyax (Zyprexa plus Prozac)
Zyprexa
Risperdal
Geodon
Clozaril

Some Anticonvulsants

Lamictal
Depakote
Carbatrol (Tegretol)

Lithium Carbonate

Click Here to See the Rankings Mood Stabilizers vs. Antidepressants

RANKING THE MOOD STABILIZERS
(Intro to Mood Stabilizers)

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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.

I have been prescribing medication since 1966. It is as much an art as it is science. When starting someone on a medication, I tell them, “I am not looking for you to say”, “doctor I think it is helping some.” What I’m looking for is “this medication is great! It has made my life better and it’s not causing any significant side effects.” Surprisingly, this is a fairly common response after a week or month or two. The harder challenge and the main goal I have is for a patient to be still saying that in 6 months, 1 year, 2 years or as long as needed. This is a much tougher test and only a few medications consistently live up to that standard. For most medications it is at best a trade off-some definite benefits but also annoying side effects.

The main factor that I use in ranking medications is my clinical experience. Everyone of my patients becomes a teacher-how does this medication help, what side effects does it have, how much difference does it make in their life, do their loved ones agree that they are doing as well as they think they are? I’m not just interested in how they feel overall, but even more importantly, how do they FUNCTION?
Many doctors get skewed feedback because the patients that don’t like the treatment just don’t come back. The ones that come back feel like the treatment is helping and so the perception is this is a good treatment. Managed care especially likes the patient that doesn’t come back. This is counted as a “one treatment cure”.

So what medications have the best batting average? This translates to what are the odds that I’m going to think this medication is great-both short term and long term?

The best medications consistently work great, have minimal side effects, and work as long as they are needed-which may mean indefinitely. I am especially biased because I don’t participate in any managed care programs. I have to get good results to keep my practice going.