While some disagree, it’s important that people understand that antipsychotics need to be used for non-psychotic depression treatment, when appropriate.
At any one time, 14 million people suffer from depression but only 60-70% of these people respond to antidepressant treatment. Of those who do not respond, 10-30% exhibit treatment-resistant symptoms including “difficulties in social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization.” Treating these people presents a huge issue for healthcare practitioners and one of the options they consider is the use of a medication class known as antipsychotics.
Recently, a group called the Therapeutics Initiative wrote a letter entitled Antipsychotics should not be used for non-psychotic depression. Their conclusions are as the title suggests: this body found little evidence to support the use of antipsychotics in the treatment of non-psychotic major depressive disorder.
And while I respect the work of this body and while they have considered some evidence (in the case of quetiapine [Seroquel], an antipsychotic), there is more to consider on the issue.
I’m always going on and on about how there are only two medications approved to treat bipolar depression (quetiapine and a fluoxetine/olanzapine combination) and about how we need new, novel ways of treating depression in bipolar disorder.
Well, this might not be novel, but it is new.
Lurasidone (Latuda) has now been approved both as monotherapy and as adjunct therapy (with lithium or valproate) in the treatment of bipolar depression by the Food and Drug Administration (FDA). Lurasidone was tested and approved for people with bipolar I.
Recently, I wrote a piece for PsychCentral that outlined some recommendations for treatment-resistant bipolar disorder. This piece talked about first-line and second-line agents for the treatment of bipolar disorder but I wanted to delve a little further into the novel agents that are now being studied for the treatment of bipolar depression. These are medications that are not typically used to treat bipolar disorder, work in new ways and show promise in recent studies. This is cutting edge and if you’re treatment-resistant this is an area that can offer you hope.
Why Are Novel Agents Needed in the Treatment of Bipolar Depression?
The reason why this piece is about unusual bipolar depression medication and not medication for mania is because the medications we have for mania are quite effective for most people. It is the bipolar depression that, typically, is very hard to treat. Additionally the two Food and Drug Administration (FDA)-approved bipolar depression treatments (quetiapine and an olanzapine/fluoxetine combination) tend to carry very serious side effects like weight gain, risk of diabetes including diabetic ketoacidosis and others. We also know that most people with bipolar disorder spend vastly more time in a depressed state than in a manic state.
According to Dr. Prakash Masand, CEO and founder of Global Medical Education, “Less than 30% of bipolar patients achieve remission that is maintained long term. There are great unmet needs in the treatment of bipolar depression. Innovative approaches are needed rather than ‘me-too’ agents that offer little incremental benefit.”
Dr. Masand notes the following are new, novel agents that look promising in the treatment of bipolar depression.
If you’re not following the Bipolar Burble blog on Facebook, you likely missed it but we had quite a conversation last night about an image that’s going around Facebook. The image says, “STOP PSYCHIATRIC DRUGGING OF KIDS.” The image is of an innocent, sweet-faced child holding up a sign with the words. The image is attributed to a user on Facebook whose political views are listed as “anarchism.”
Regardless as to who made this image, the image itself has been circulating in, you guessed it, antipsychiatry circles. (I won’t bother drawing lines between antipsychiatry and anarchism, but, you know, I probably could.)
Not surprisingly, one reader with a mentally ill child took offence to this image and all the passing around of it.
This image suggests that:
- Giving psychiatric medication to children constitutes “drugging”
- Parents shouldn’t be giving their children medication
- Children shouldn’t be taking medication
- Parents who give their children medication are doing something wrong
In other words, it stigmatizes both parents of, and mentally ill children themselves.
In other words it spreads negativity, hate and prejudice.
Again, a commenter last night popped onto the blog to tell me how psychiatric medications “do more harm than good” and how “I [the commenter] know for a fact that these meds no not work.”
I’m not sure how so many people confuse “fact” with “opinion.” It is the opinion of some people that psychiatric medications don’t work. It is the opinion of some people that psychiatric medications do more harm than good.
I am not of that opinion. And I actually have facts on my side.
I have been known to lament that there’s nothing new under the sun when it comes to depression treatment, and thus, there is little hope for people with true treatment-resistant depression. (And by treatment-resistant depression I mean people who really have tried everything, and there are few in this category.)
But I forget how far we’ve come and how fast. It isn’t fair to say there aren’t new approaches to treatment-resistant depression because there are new approaches being researched and approved every year. Here are a few noted by Current Psychiatry article Innovative approaches to treatment-resistant depression:
I’m a pretty busy gal right now, so not a lot of time to write new material. I promise I’ll try to get to something new next week.
- Last Minute Holiday Tips for the Bipolar – just published today. Here are four things you should know before you get any deeper into the holidays.
- What 2011 Taught us About Mental Illness – a wrap-up of the top ten things research taught us about mental illness last year including: bipolar misdiagnosis, bipolar treatment success predictor, mania treatment comparison and antipsychotic information. Part one and part two.
- You’re Narcissistic! Getting Over Insults – How one reader got to me even though I knew they shouldn’t have.
- Celebrating Mental Health News – on why we should celebrate the good moments in mental illness.
- How to Choose a Good Psychiatrist – one I’ve touched on here but in more detail.
- Bipolar Disorder Thought Types – have you ever considered the odd types of thoughts you have a person with a mental illness? I have.
- The Importance of Self-Care in Bipolar Disorder – tips on self-care plus a video.
- Sexual Health and Bipolar Disorder – the sexual concerns of people with mental illness.
Last week I didn’t post three new things but don’t take that to mean I wasn’t learning because I certain was, and always am. For this week I have these three new pieces of information to share:
- Repetitive transcranial magnetic stimulation (rTMS) treatment for depression to be free for (some) Canadians
- Brain changes are noted in depressed females
- Why are some doctors anti-benzodiazepine?
1. Free rTMS in Manitoba (Canada)
RTMS stands for repetitive transcranial magnetic stimulation and is a treatment for treatment-resistant depression. RTMS is considered a neurostimulation therapy, like electroconvulsive therapy (ECT), but is non-invasive. RTMS has its pros and its cons.
- Pros – rTMS is drug-free, has few side-effects and can produce remission from depression in some people
- Cons – rTMS is expensive, intensive and its therapeutic effects are generally temporary
Cost of RTMS
Most people don’t get rTMS due to the cost. Repetitive transcranial magnetic stimulation requires 2 sessions per day for 10 days (weekends off) plus and additional possible 5-10 sessions depending on the reaction to treatment. Needless to say, this is one expensive therapy. In Canada that works out to $5000 – $7500 and in the States lord only knows how much.
And Manitoba is taking the very civilized step forward of offering rTMS as part of the public health care system, which is how it should be. The only reason why it isn’t is cost. You can get rTMS in Canada, but this is the first time I’ve heard of it being free.
Congratulations to Manitoba for taking a step forward in helping people with a mental illness. I hope this is the sign of things to come across the country.
2. Brain Changes Noted in Depressed Females
Women are twice as likely to develop depression as men but no one knows why. This study takes a look at female brains to look for biological identifying markers between depressed brains and well brains.
. . . depressed women had a pattern of reduced expression of certain genes, including the one for brain-derived neurotrophic factor (BDNF), and of genes that are typically present in particular subtypes of brain cells, or neurons, that express the neurotransmitter gamma-aminobutyric acid (GABA.) These findings were observed in the amygdala, which is a brain region that is involved in sensing and expressing emotion.
BDNF and GABA in Depressed Brains of Women
BDNF is something I’ve mentioned before as to a biological cause of depression. Yes, just another fact to chalk up for all the people saying depression is just “in your head.”
And work toward identifying the gene that contributes to depression:
. . . researchers tested mice engineered to carry different mutations in the BDNF gene to see its impact on the GABA cells. They found two mutations that led to the same deficit in the GABA subtype and that also mirrored other changes seen in the human depressed brain.
I keep telling people: We’re getting closer to effective treatments and understanding every day.
3. The Religion of Benzodiazepines – Why Some Doctors Don’t Prescribe Benzos
I’ve taken benzodiazepines (benzos) of one type or another for a decade and never once had a problem with them, but many people do develop tolerance, dependence and drug-seeking behavior around this type of medication.
My opinion is that benzodiazepine medications can be used quite safely when properly handled, but that some people have the tendency to get addicted to medications, and for them, these medications may be contraindicated. In other words, it’s down to the individual and prescription of benzos cannot be characterized as “bad” or “good” in a blanket statement.
I plan on writing a whole article about this, but if you’d like a sneak peek about why some doctors are anti-benzodiazepine, check out this article in Psychiatric Times.
Until next week all, when I shall learn more and do better.
You may not know this, but ecstasy (MDMA) has been studied as a psychiatric medication. Yes, that’s right, that stuff kids take at raves. The stuff that makes you thirsty and fall in love to the person next to you. That stuff. And MDMA was shown effective in several psychiatric uses.
But research on MDMA (ecstasy) was curtailed in 1985 when the US government named it a class 1 drug (like heroin) over the objections of doctors. Psychiatric research on MDMA is gearing up again though and it has shown promise in treating post-traumatic stress disorder (PTSD) and possibly depression and anxiety.
What is Ecstasy (MDMA)?
The active substance in ecstasy is MDMA (3,4-methylenedioxymethamphetamine). However, when ecstasy is purchased on the street, MDMA is common mixed with methamphetamines and other drugs.
So, to be clear, this means that while taking MDMA in a clinical setting may pose limited risk, taking it illicitly is a different risk profile altogether. I do not recommend you buy ecstasy off the street to treat mental illness. (Particularly if you suffer from bipolar 1 or any psychotic symptoms.)
The subjective effects of ecstasy (MDMA) are produced, in part, by a huge release of serotonin. This may be responsible for reducing the perception of threats and of negative emotions in others.
Ecstasy, MDMA, also increases levels of the neurohormones oxytocin, prolactin and cortisol. Oxytocin is thought to reduce feelings of fear and increase social affiliation and trust while cortisol is a stress hormone which may explain why some people experience anxiety while using MDMA.
How is Ecstasy (MDMA) Used in Psychiatry?
Interestingly, ecstasy is being used during psychotherapy and not as a psychopharmacological treatment, per se. MDMA is administered during elongated therapy sessions (8 hours) and patients work through emotions and memories that were impossible to handle beforehand. Two or three MDMA treatment sessions may be done with preparation therapy sessions beforehand and follow-up therapy sessions after.
“. . . enhanced self-understanding [and] insight into personal patterns or problems, greater self-confidence or self-acceptance, lowered defenses [while] undergoing a therapeutic emotional process,” and “less negative thoughts or feelings.”
Studies on MDMA
Right now all the studies are on MDMA-treatment of post-traumatic stress disorder (PTSD) but look for other studies in the future. These studies on PTSD and ecstasy (MDMA) look extremely promising. Right now, several countries have completed phase one research and are onto phase two.
Risks of MDMA in Psychiatry
Risks vary depending on who you ask but in controlled, clinical use the risks of ecstasy (MDMA) appear to be minimal. While some worry about the effects on memory and cognition, some studies have shown there is no effect to these areas. There haven’t been enough participants in studies to make conclusive statements about MDMA risks.
My Thoughts on MDMA in Psychiatry
I’m very interested in such medications. MDMA works on the brain in a powerful way that other drugs do not. In this way ecstasy is unique and is hopeful for people with treatment-resistant disorders. I have a feeling that flooding the brain in this unusual way may be helpful in improving intractable disorders. This is mostly a hunch on my part, but I look forward to seeing what the future holds.
Psychiatric Times, Does MDMA Have a Role in Clinical Psychiatry? By Michael C. Mithoefer, MD, 06 May 2011
Or other bothersome antidepressants.
Generally, following the rules I wrote about last week on how to stop antidepressants while minimizing withdrawal work, and most people can successfully withdraw from antidepressants with few side effects.
Some Antidepressants Are Hard to Get Off Of
Unfortunately, some antidepressants are not so easy to get off of no matter what you do. (You can learn more about this through http://drugabuse.com/ and other similar sites.) Some antidepressants:
- Resist a taper strategy
- Have intolerable withdrawal effects anyway *
People Have Trouble Withdrawing from these Antidepressants
Any antidepressant can feel impossible to withdraw from, but the antidepressants people have most trouble withdrawing from are:
- Paroxetine (Paxil)
- Duloxetine (Cymbalta)
- Venlafaxine (Effexor, any version)
- Desvenlafaxine (Pristiq)
But by far, venlafaxine and desvenlafaxine (Effexor and Pristiq) are the ones I hear about. In my opinion, these two drugs are a nightmare to come off of for most people. ^ (I’m not saying everyone has trouble with these antidepressants, just that many do.)
Here are tips on how to get off of horrible~ drugs like venlafaxine (Effexor) and desvenlafaxine (Pristiq).
Did I mention yet I’m not a doctor? Ah, well I’m not. None of this is to be considered medical advice; this is an informational article only. Never alter your treatment without talking to your doctor. Thanks.
As I mentioned last week, it’s very difficult to measure long-term outcomes of depression treatment due to the confounding depression variables like severity of depression, duration of depression, number of depressions and so on.
In short, the sicker you are, the more depressed you are, the more likely it is you’ll get treatment.
Antidepressant Treatment Outcomes Long-Term, A Study
I discussed the basic outcomes of this study: The association between antidepressant use and depression eight years later: A national cohort study by Colman et al. (you may have to select Science Direct to see the study, you don’t need a subscription) which tries to take these variables into account.
Colman et al. showed those who took antidepressants had better depression treatment outcomes than those who didn’t, eight years later, once confounding variables were taken into consideration.
I’ll now point out the strengths and weaknesses of this study as well as some other interesting tidbits shown or cited in the study. Oh, and I’ll give my opinion on what it all means.
Strengths of this Depression Treatment Outcome Study
No study, of course is perfect, but each has its strengths. In the case of this study on depression treatment outcomes, some of the strengths include:
- An attempt to quantify and account for factors we know will affect treatment outcomes
- Study uses a large, heterogeneous, real-life, population base
- Quality, fairly comprehensive data available
- Replicated findings of a British study involving anxiolytics (anti-anxiety medication) and antidepressants
Weaknesses of this Depression Treatment Outcomes Study
Weaknesses mostly bias the outcome towards the conservative. In other words, the relationship between antidepressant use and a positive long-term outcome may be stronger than reported.
- Does not have 100% data over eight years (Those who dropped out had worse depressions. This biases the data likely indicating a stronger relationship than shown.)
- Not a randomized controlled trial (not likely possible)
- Does not capture comorbid (co-occurring) disorders (likely indicating a stronger relationship than shown)
- Does not specifically capturing other treatments*
- Didn’t control for perception of need for treatment. In other words, those who were able to identify the need for, and seek, treatment took antidepressants and had better outcomes. So a factor then would be the person’s treatment-seeking behavior.
For all the nitty gritty on the strengths and weaknesses of this depression treatment outcome study, see here.
Outcomes of Antidepressant Treatment of Depression, Facts
In addition to their main findings, here are some other interesting depression treatment outcome facts either shown or referenced in the study:
- Antidepressants are particularly useful for those with severe symptoms
- Of 285 depressed patients, those using higher levels of antidepressants were significantly more likely to recover from symptoms in the short term (from a 20-year study)
- British study found that of 204 depressed patients, those using antidepressants or anxiolytics (anti-anxiety medication) were significantly less likely to be suffering from symptoms of depression ten years later
- Maintenance use of antidepressants has been shown to reduce future depressions
- Those with partial remission (still having some depression symptoms) are far more likely to experience future depressions
- The longer depressive symptoms persist before treatment the worse the long-term prognosis
- The most strongly correlated value to better outcome was recent antidepressant use
Because I knew you’d want to know (I did too):
Funding for this longitudinal depression treatment outcome study was provided by government, grant and award money. Study was cleared through the Health Research Ethics Board of the University of Alberta.
So Long-Term Antidepressant Use is Good?
Well, I can’t say that. What I can say is this study is suggestive^ of the fact that people who are depressed and take antidepressants do better over the long-term than those who don’t. But remember:
- People weren’t necessarily on antidepressants the whole eight years.
- The key (shown in studies and in my opinion) is to treat the depression as soon as possible and get all symptoms into remission.
So, that doesn’t mean get and stay on antidepressants forever, nor does it mean go on and off antidepressants. Those are individual choices depending on the person’s situation. If you can achieve #2 then your prognosis (in my opinion) is very good. And generally this is done with antidepressants, but depending on your personal situation, you may be able to achieve it through other means.
This also shows people taking antidepressants don’t do worse. This matters because there is a meme out there that taking antidepressants will somehow eat your brain and create mental illness.** This study suggests not.
A Little Bit More
* Study also talks about the role of therapy in depression treatment but no relationship was found between those who got therapy and those that had more positive outcome, suggesting there was no benefit to therapy. However, this is likely due to the broad definition of the word “therapy.” This is why I chose to omit information therapy findings.
^ This is not a causational relationship (where we know one thing causes another) as causation is hard to ascertain without real double-blind placebo controlled randomized study. And we don’t have that.
** Antidepressants actually increase the creation of neurons (neurogenesis) and increase brain volume.
Long (long) time readers will recall that once-upon-a-time I took the atypical antipsychotic Geodon. I found this to be an unbearably painful and side effect laden psych med. I hated Geodon. I wouldn’t wish Geodon on my worst enemy. I lost touch with reality on Geodon. I passed out at work on Geodon. I got sick constantly on Geodon.
You know, that being said, Geodon works for a lot of people.
I gather my reaction to this antipsychotic was fairly atypical. And if I had known what to eat when taking Geodon that might have helped.
Geodon (generic ziprasidone, also marketed as Zeldox by Pfizer) was the fifth atypical antipsychotic to receive FDA approval, in 2001. Geodon is approved to treat schizophrenia, bipolar disorder mixed-states and bipolar mania. And, of course, Geodon is prescribed off label in other cases of bipolar disorder or for depression.
Facts about the Atypical Antipsychotic Geodon
Interesting facts about atypical antipsychotic Geodon:
- Has a very short half-life – a mean of 2-5 hours
- Geodon should always be taken with food (see below)
- It slightly increases the QTc interval (heart rhythm)
- Geodon can occasionally cause mania in people with bipolar disorder
It has all the other nasty effects that atypical antipsychotics do like weight gain, diabetes, tardive dyskinesia and the like.
Geodon Must be Taken with Food
One of the nasty problems I had with Geodon is that I found unless I ate exactly the right thing (red meat, I found, but results were variable) I would get really sick after taking the drug. I would feel nauseated, dizzy, crazy and basically so sick I had to go to sleep. And it was really hard to predict exactly when this would happen. It was a bitch.
Food with Geodon Affects Bioavailability
What I didn’t know is what really matters is the number of calories consumed with Geodon.
I had thought taking the Geodon was making me sick but actually it was the withdrawal from Geodon making me sick. Due to the short half-life, if I didn’t get the correct dose of Geodon, I went through withdrawal. (I took it once a day, increasing the problem.)
And as it turns out, if you don’t eat the right food, Geodon isn’t properly absorbed into your bloodstream. This is known as bioavailability. If you take Geodon without food its bioavailability may only be 50%. So 200mg becomes 100mg.
What to Eat with Geodon
While psychiatrists generally tell people to take Geodon with food, I doubt anyone mentions that if you don’t, it is only half as useful.
Luckily, there’s a study. According to The impact of calories and fat content of meals on oral Ziprasidone [Geodon] absorption: a randomized, open-label, crossover trial:
- Maximum Geodon absorption was seen with meals of 1000 calories
- Low-calorie meals of 250 calories had only a 60% – 90% absorption rate, highly variable
- Meals of 500 calories were close to the absorption rate of the 1000 calorie meals
- Meals of 500 – 1000 calories had much less variable Geodon absorption rates
- Fat content of the meal had no bearing on outcome
So, in short, if you’re taking Geodon, you should eat a meal of 500 calories or more when you take your Geodon.
Isn’t That a Lot of Calories?
I’d say so, yes. Seeing as dosage instructions for Geodon are to take Geodon twice daily with food, that’s at least 1000 calories right there. Kind of nutty, but there it is.
Do Doctors Know about Calories, Diet and Geodon?
Honestly, I have no idea. I wouldn’t be surprised if they didn’t know the magic formula was 500 calorie meals with Geodon. You might want to ask your doctor about it.
 In case you’re curious, Geodon is one of four drugs Pfizer plead guilty to illegally promoting for disorders for which it was not FDA approved.
 By the way, you could get around this problem with intramuscular injections. If, you know, that were an option for you.
 And by “should” I mean according to the study and after talking to your doctor. Of course.