One of those things was eat ice cream. A lot. So I gained a few pounds. It was time to buy new pants anyway. The only important thing was that my medicine was working and I was feeling good. I felt like participating in my life again. Feeling good and eating ice cream were natural.

But then I broke the couch.

Maybe it was a coincidence that I was the one whose bottom touched the couch and made it go POP and collapse. But it had occurred to me, in that moment I felt the couch break underneath me, that I had gained a lot of weight. And that was enough to tell me that all this weight gain was starting to bother me.

I finally realized that as my mood had gone up, so had my weight; maybe my medicine came with a trade-off. I’d never had a medicine that made me gain weight before or gave me cravings that led to weight gain. But here I was.

I’d always told people in the same situation that it didn’t matter if they gained weight. Obviously mental health is more important than gaining a few pounds.

But is there a line that can get crossed, where weight gain can make the scales tip in favor of switching meds? What’s the number? 15 pounds? 25 pounds? 30 pounds? 50 pounds? In what span of time? One month, three months, a year? What is OK and not OK?

Mental health is most important, but at what point does weight gain also affect health? It affects physical health, like blood pressure and risk factors that come with obesity (I am now technically obese), but I’m not even talking about the physical drawbacks of weight gain. What I’m irrationally worried about is the emotional toll that weight gain can cause.

I’m not satisfied with what the medicine is doing with my body. I don’t feel like myself. I feel like myself when I was pregnant, only without a baby, meaning I feel too big and tired and slow. That is affecting my mental health. Not in a serious, clinical way. But in a way that is still real.

Still, I would never stop a drug that’s working in favor of nothing, or one that didn’t work, to be able to lose weight. I’ve been in the dark hole that depression is, and there’s no way I would jeopardize my own quality of life or my family’s with my vanity. But it’s a little tempting, when I’m still on my meds and they’re working well, but there’s just this one side effect…. And I think, maybe I could stop. But I wouldn’t just stop; I would switch to something else, after talking with my doctor like I should. I’m more vain than I realized, but I’m also even more terrified of falling into depression again.

One of the most disconcerting things is the feeling that I don’t have power over my body. Even when I eat well, and exercise, and sweat off what feels like pounds of water, it turns out I have actually gained weight. I haven’t lost a single pound since I started my medicine several months ago. That unsettles me and makes me feel a tiny bit like I do in a depressed state: I am not in control of my body.

This doesn’t cause me to lose hope in general, to think that there won’t be a better time. But it does cause me to lose confidence in myself. I’m already on shaky ground, living with mental illness. Will I feel good today or bad? How am I feeling? But now, I add, How do I look? How much have I gained? to the daily evaluations. I can’t always depend on my mind; now I can’t depend on my body.

Having a mental illness throws new challenges at me at every turn. Even when I feel well, it still reminds me of its presence, in this case, through these extra pounds clinging to me. I believe that there might be side effects and trade-offs to medication, but I also believe they saved my life, or at least saved the quality of my life, and that it’s worth it. And I believe the perfect medication might be out there, waiting to still be discovered for me.

Maybe I’ll always have to make the decision between effective medicine and side effects like weight gain. But I have hope that someday I won’t have to.

The mental health charity Mind UK recently highlighted their concern that there is a serious need for a range of therapies to be made available to depression sufferers.

According to the best psychological working practices, medication is now considered to be only one option for effectively treating the illness.

Talk therapies — otherwise known as psychotherapy — such as cognitive behavioral therapy (CBT) have proven effective at alleviating melancholic symptoms in hundreds of research studies conducted around the world. In Australia, the Australian Psychological Society has identified a serious need for psychotherapeutic interventions in the lives of people with depression.

Cognitive behavioral therapy (CBT) is a form of psychotherapy. Participants work with a specially trained psychologist to make positive steps in changing their thoughts and feelings. Committing to CBT means accepting that your actions affect your emotions and reasoning. Therapists help you to learn skills and strategies for changing negative thinking. This helps many people to learn to cope with depressive illness.

A recent study in the UK, carried out over a period of 12 months, looked at the benefits of CBT for managing depression. Participants were allocated a one-hour CBT session each week for the period of the trial.

After six months, 46 percent of the group who had been previously resistant to medication reported a reduction in depressive symptoms. The study concluded that CBT can improve quality of life by reducing depression’s severity.

A 2012 study published in the Australian and New Zealand Journal of Psychiatry involved a review of Australian National Health data. Researchers became interested in the period between 2001 and 2006, when better access to psychological treatment was made available in Australia.

The study showed from 2001 to 2008, following health care reform, there was a drop in the use of antidepressant and anti-anxiety medications. CBT is currently recognized in Australia as being a viable and effective way of treating mental illnesses like depression.

It is important to note that CBT is not intended to be a substitute for medication. In many cases it will serve to complement any medicine from the family doctor or psychiatrist. However, in those for whom medication has failed, CBT offers an alternative while new medicines are being developed. Of course, not everything — whether medication or talk therapy — will work for everyone.

In Australia, there is still a shortage of psychiatrists. The right of psychologists to prescribe medication is now a subject for debate. If this becomes reality, the therapist will then be able to evaluate each patient’s needs, and only prescribe drugs when necessary.

In the meantime, although it may not be the best option, family physicians are able to prescribe psychiatric medications if they believe it warranted.

If it were actually effective, I would wholeheartedly join you in your strike against shame, holding signs to keep it out of the psyche and saying, “Shame on you, shame.” But from my experience, it usually just grows into an angry beast. It haunts us day and night until we do something about it.

Pushing away the shame isn’t the answer. So what is?

Sharing the shame with a trusted person is what will heal us.

Think of a time when you have felt shame. Maybe the shame is associated with a word, a fantasy or thought, or an action. Here are some:

• “I put on a good facade, as if I have everything together. But I break down and cry when no one is around.”
• “I am broke.”
• “I think about cheating on my husband.”
• “I have cheated on my husband.”
• “I am married to a woman but I am more attracted to men.”
• “I have a mental illness.”
• “I was abused as a child.”
• “I am a battered woman.”
• “I hate the way I look.”
• “I hate my kids sometimes.”
• “I cheat to get good grades in school.”
• “I got fired.”
• “I lied about my age.”
• “I dropped out of school.”
• “My family was on welfare.”
• “I have STDs.”
• “I have AIDS.”
• “I prostituted for money.”
• “I used to steal when I was a kid. I still do.”
• “I have an addiction.”
• “I take medication for my depression.”
• “I dream big but I am lazy.”

If you keep shame inside, it will produce a heavy sensation in your body. But notice what happens when you share it with someone you trust, someone who will not judge you. Most likely, it will be embarrassing at first. But once you share that same story over and over again, the shame will be able to go through transformation.

Ultimately, the shame will no longer have the same power over you. Eventually, you will be able to look back and say to yourself, “I can’t believe that I was so ashamed about that.”

Try using imagery to help you. Imagine shame to be a baby who just looks terrified on the outside but frightened on the inside, sucking on her thumb. Be curious about what this baby is so terrified about. Move toward it and ask it what it needs. Hold it in your arms with great care, curiosity and empathy.

When you give shame attention, you free yourself from being held in captivity. You will be able to feel joy again and walk with confidence. It is the act of letting yourself be who you are that frees you from the pain associated with shame. It is also an ingredient for healthy self-esteem. You will eventually learn that you aren’t such a bad person after all.

“Most psychiatric drugs in use today originated in serendipitous discoveries made many decades ago,” according to a recent article on Science News by Laura Sanders. And it’s true — we can trace back today’s most popular psychiatric drugs to discoveries made over 30 — and in some cases, 40! — years ago.

Because of the heady cost of drug development — costing hundreds of millions of dollars to bring a new drug to market — most pharmaceutical companies have been playing it safe these past few decades. They’ve been working on developing “me too” drugs — subtle molecular changes to existing compounds.

Which means the pipeline is darned near empty of truly new drugs likely to come out in the next 5 to 10 years for the most common types of mental illness.

This provides the drug company with two things. The first is a new medicine they can patent and sell at a significant markup over the old, generic drug it’s based off of. The second is the illusion of progress, of releasing something that is “new and better” than the old thing — but which additional research almost always demonstrates is simply as good — not better — than the old thing (and usually with a different — not better — side effect profile).

So the “new” SSRIs of the 1990s did away with tricyclics’ side effects, but brought on a whole host of their own, new side effects (chief among these, sexual dysfunction… as though nobody cared much about the quality of their sex lives).

The one thing these “me too” drugs don’t provide is any additional, substantial relief to patients.

So it should come as no surprise that most pharmaceutical companies’ psychiatric drug pipelines are… how shall we say?… empty.

Not a single drug designed to treat a psychiatric illness in a novel way has reached patients in more than 30 years, argues psychiatrist Christian Fibiger of the University of British Columbia in Kelowna, who described the problem in a 2012 Schizophrenia Bulletin editorial. “For me, the data are in,” says Fibiger, who has developed drugs at several major pharmaceutical companies.

“We’ve got to change. This isn’t working.”

The biggest problem, from mine and other researchers’ perspective, is the simple lack of understanding of the organ we’re trying to impact with these drugs — the brain.

Perhaps the largest impediment to the development of new psychiatric drugs is the brain itself. A complex web of interconnected systems constantly altered by the environment, the brain is difficult to study.

Even though it’s nestled right in our heads, the brain is hard to reach. A blood pressure cuff can be slapped on for an instant and objective measure of what’s happening with the heart. A needle biopsy can physically pull out suspected breast cancer cells for further tests. But when it comes to the brain, there is no easy way to identify and measure the thing that isn’t working.

As neuroscientist Steven Hyman of the Broad Institute of MIT and Harvard says in the article, “You can’t just open up the hood, take out a chunk and see what’s happening.”

Thomas Insel, director of the National Institute of Mental Health, believes there is hope by pursuing a new path in research — understanding the very basics of the brain’s functioning. Combined with Obama’s announcement of the Brain Activity Map project to be undertaken by the U.S. later this year, there is hope that we can greatly increase our understanding of the body’s most vital organ.

The situation is grim, but not hopeless, says Insel. At a time when major pharmaceutical companies are abandoning psychiatric drug development, Insel says he is doubling down, investing federal grant money in places where investors fear to tread.

“There are a whole series of pretty amazing developments that I think are worth investing in,” he says.

That’s the good news… But it’s going to take years — and more likely, decades — before we will see the benefit of such research efforts.

But it Hasn’t Stopped Drug Sales…

But that hasn’t stopped the sales of all of these me-too psychiatric drugs:

Which only goes to show you that pharmaceutical company marketing works better than perhaps some would give it credit for.

Read the full Science News article (lengthy, but gives many examples and further details about this issue): No New Meds

Much harder than most physicians and many psychiatrists are willing to admit.

That’s because most physicians — including psychiatrists — have not had first-hand experience in withdrawing from a psychiatric drug. All they know is what the research says, and what they hear from their other patients.

While the research literature is full of studies looking at the withdrawal effects of tobacco, caffeine, stimulants, and illicit drugs, there are comparatively fewer studies that examine the withdrawal effects of psychiatric drugs. Here’s what we know…

Benzodiazepine withdrawal has a bigger research base than most classes of medications — SSRI withdrawal has much less research. So what’s that research say? Some patients are going to have an extremely difficult and lengthy time trying to get off of the psychiatric drug prescribed to them. Which ones? We don’t know.

One study nicely summarizes the problem experienced in many such patients:

Various reports and controlled studies show that, in some patients interrupting treatment with selective serotonin reuptake inhibitors or serotonin and noradrenaline re-uptake inhibitors, symptoms develop which cannot be attributed to rebound of their underlying condition. These symptoms are variable and patient-specific, rather than drug specific, but occur more with some drugs than others. [...]

There is no specific treatment other than reintroduction of the drug or substitution with a similar drug. The syndrome usually resolves in days or weeks, even if untreated. Current practice is to gradually withdraw drugs like paroxetine and venlafaxine, but even with extremely slow tapering, some patients will develop some symptoms or will be unable to completely discontinue the drug.

Psychiatrists and other mental health professionals have known ever since the introduction of Prozac that getting off of benzodiazepines or the “modern” antidepressants (and now add the atypical antipsychotics too) can be harder than getting symptom relief from them. Yet some psychiatrists — and many primary care physicians — appear to be in denial (or are simply ignorant) about this problem.

Back in 1997, a review of the literature on SSRIs (selective serotonin receptor inhibitors) outlined the problem (Therrien, & Markowitz, 1997):

Presents a review of 1985–96 literature on withdrawal symptoms emerging following the discontinuation of selective serotonin reuptake inhibitor (SSRIs) antidepressants. 46 case reports and 2 drug discontinuation studies were retrieved from a MEDLINE search.

All of the selective serotonin reuptake inhibitors were implicated in withdrawal reactions, with paroxetine most often cited in case reports. Withdrawal reactions were characterized most commonly by dizziness, fatigue/weakness, nausea, headache, myalgias and paresthesias.

The occurrence of withdrawal did not appear to be related to dose or treatment duration. Symptoms generally appeared 1–4 days after drug discontinuation, and persisted for up to 25 days. [...]

It is concluded that all of the SSRIs can produce withdrawal symptoms and if discontinued, they should be tapered over 1–2 weeks to minimize this possibility.

Some patients may require a more extended tapering period. No specific treatment for severe withdrawal symptoms is recommended beyond reinstitution of the antidepressant with subsequent gradual tapering as tolerated.

The conclusion is quite clear — some patients are going to suffer from more severe withdrawal effects than others. And, just like psychiatry has no idea which drug is going to work with which patient and at what dose (unless there’s a prior medication history), psychiatry also can’t tell you a damned thing about whether a patient is going to have difficulty getting off of the drug when treatment is completed.

It’s simple trial and error — every patient that enters a psychiatrist’s office is their own personal guinea pig. That is to say, you are your own personal experiment in finding out what drug is going to work for you (assuming you’ve never been on a psychiatric drug in the past). Our scientific knowledge hasn’t yet advanced to be able to tell what drug is going to work best for you, with the least amount of side or withdrawal effects.

The U.S. Food and Drug Administration (FDA) doesn’t require pharmaceutical companies to conduct withdrawal studies in order to analyze a drug’s impact when it’s time to discontinue it. It only requires a broader safety evaluation, and a measure of the drug’s efficacy. The FDA is concerned about adverse events while a patient is taking the drug — not adverse events when the drug is removed. In recent years, some have been calling on the FDA to require pharmaceutical companies to conduct more analysis on a drug’s discontinuation profile, so that the public and researchers can get a clearer picture.

While all SSRIs have these problems, two drugs in particular appear to stand out in what little research is out there — Paxil (paroxetine) and Effexor (venlafaxine). The Internet is littered with horror stories of people trying to discontinue one of these two drugs.

And they’re not alone — benzodiazepines can also be extremely difficult to stop. “Withdrawal reactions to selective serotonin re‐uptake inhibitors appear to be similar to those for benzodiazepines,” says researchers Nielsen et al. (2012).¹

What Do You Do About Withdrawal?

Most people are prescribed a psychiatric medication because it’s needed to help alleviate the symptoms of a mental illness. Not taking the medication is often simply not an option — at least until the symptoms are relieved (which often can take months, or even years). Psychotherapy, too, can often help not only with the primary symptoms of mental illness, but also as a coping mechanism during medication withdrawal.²

The important thing is to go into the process with your eyes wide open, understanding the potential that discontinuing the medication may be difficult and painful. A very slow titration schedule — over a period of multiple months — can sometimes help, but may not always be enough. In some extreme cases, a specialist who focuses on helping people discontinue psychiatric drugs might prove helpful.

I wouldn’t let the problems with withdrawing from some of these medications prevent me from taking the drug in the first place.

But I would want to know about it beforehand. And I’d want to be working with a caring, thoughtful psychiatrist who not only acknowledged the potential problem, but was proactive in helping his or her patients deal with it. I would run — not walk — away from a psychiatrist or physician who claimed the problem didn’t exist, or that I shouldn’t worry about it.

This article was edited to clarify a few sentences on Feb. 14, 2013.

References

Kotzalidis, G.D. et al. (2007). The adult SSRI/SNRI withdrawal syndrome: A clinically heterogeneous entity. Clinical Neuropsychiatry: Journal of Treatment Evaluation, 4, 61-75.

Nielsen, M., Hansen, E.H., & Gøtzsche, P.C. (2012). What is the difference between dependence and withdrawal reactions? A comparison of benzodiazepines and selective serotonin re-uptake inhibitors. Addiction, 107, 900-908.

Therrien, F. & Markowitz, J.S. (1997). Selective serotonin reuptake inhibitors and withdrawal symptoms: A review of the literature. Human Psychopharmacology: Clinical and Experimental, 12, 309-323.

1. Thanks to Beyond Meds for the suggestion of this blog topic.
2. Tellingly, I could find no similar withdrawal syndrome associated with leaving psychotherapy, although certainly some people have difficulty with ending psychotherapy.

But electroconvulsive therapy (ECT) treatment has developed considerably since the days depicted in “One Flew Over the Cuckoo’s Nest.”  A current study at JAMA Psychiatry examines a treatment called transcranial Direct Current Stimulation (tDCS).

Could this fairly new form of electrical treatment for depression really be effective — and without the negative side effects of ECT?

This new treatment, which involves stimulating the brain with a weak electrical current, is starting to be considered as an alternative — and potentially effective — treatment for depression.  tDCS, unlike traditional ECT, passes only a weak electrical current into the front of the brain through electrodes on the scalp.

Patients receive the treatment once a day for 30 minutes and remain awake and alert during the entire procedure.

Why is New Treatment for Depression So Essential?

Depression in adulthood remains a common and often under-treated condition.

Depression can occur at any age, but it typically emerges in the mid-20s. Women experience depression twice as frequently as men, and symptoms can vary from mild to severe. Major depressive disorder, which may be diagnosed when depressive symptoms last for 2 weeks or more, is understood to occur in 15 to 17 percent of the population.

Symptoms of major depressive disorder can include a depressed mood, loss of interest and enjoyment, reduced energy, increased fatigue, diminished activity and reduced concentration and attention.

These and other symptoms, particularly when prolonged, impair a person’s ability to function in day-to-day life, making effective treatment essential.

Research continues to improve our knowledge about the impact of depression on our ability to process information and the underlying processes in the brain that are associated with depressive symptoms.

With increased information, psychologists and mental health professionals have made significant progress in identifying effective treatments.  A combination of cognitive behavioral therapy and medication has evolved the most effective treatment to date.

However, it is not fully understood exactly how and why antidepressants work. And despite significant advancements in medications, treating major depressive disorder remains a challenge. Although medication helps, it can be costly and produce troublesome side effects.

Recent Advances in Electrical Treatments

Noninvasive brain stimulation, such as tDCS, has been increasingly investigated for the treatment of major depression.

In previous research out of the University of New South Wales (UNSW) and the Black Dog Institute, 64 depressed participants who had not benefited from at least two other depression treatments received active or sham tDCS for 20 minutes every day for up to six weeks.

The study found up to half of depressed participants experienced substantial improvements after receiving the treatment.

In a recent clinical trial, Andre R. Brunoni, M.D., Ph.D., of the University of Sao Paulo, Brazil, and colleagues examined the safety and efficacy of electrical current therapy compared to treatment with sertraline hydrochloride for major depressive disorder (JAMA Psychiatry).

Participants included 120 patients with moderate to severe nonpsychotic unipolar major depressive disorder who were not taking antidepressant medications. A three-point change in a depressive rating scale at the six-week mark was considered clinically significant.

Participants were divided into groups to compare sertraline to tDCS or a combination of both.

In major depressive disorder “the combination of tDCS and sertraline increases the efficacy of each treatment. The efficacy and safety of tDCS and sertraline did not differ,” the study concludes.

According to the study reports as noted in JAMA Psychiatry, there was a significant difference in the depression rating scale score when comparing the combined treatment group (sertraline/active tDCS) vs. sertraline only (mean difference 8.5 points); tDCS only (mean difference, 5.9 points); and placebo/sham tDCS (mean difference 11.5 points).

Side effects of participants who received active tDCS treatment were fairly minimal, with skin redness at the treatment site and an increased potential for hypomania or mania episodes being the primary adverse effects.

More research is needed to confirm the results of this latest study. But increasingly, it looks like tDCS may offer people with depression another alternative to more traditional forms of treatment.

Reference

Andre R. Brunoni MD, PhD, Leandro Valiengo MD, Alessandra Baccaro BA, Tamires A. Zanão BS, Janaina F. de Oliveira BS, Alessandra Goulart MD, PhD, Paulo S. Boggio PhD, Paulo A. Lotufo MD, PhD, Isabela M. Benseñor MD, PhD, Felipe Fregni MD, PhD. The Sertraline vs Electrical Current Therapy for Treating Depression Clinical Study: Results From a Factorial, Randomized, Controlled Trial. (2013). Arch Gen Psychiatry, 70, 1-9. doi:10.1001/2013.jamapsychiatry.32

Now, if you’re not someone who has struggled with chronic depression, those stats won’t warrant a happy dance.

But if you’re someone like myself, who assesses her mood before her eyes are open in the morning, hoping to God that the crippling anxiety isn’t there, then those numbers will have you singing Hallelujah.

They are better than the statistics released by a large, six-year, four-step government study called the Sequenced Treatment Alternatives to Relieve Depression trial, or STAR*D. STAR*D looked at the use of popular antidepressants in people with chronic, severe depression who do not respond to a particular drug and may suffer from multiple mental and physical disorders.

The researchers found that trying treatment options such as adding a second drug to a SSRI, switching to a new drug or a different class of drug, and waiting a full 12 weeks to assess results can lead to remission in symptoms in up to half of patients.

That’s not much to celebrate, in my opinion. Good news, but not great.

Folks trudging through the everyday muck of depression and pervasive, annoying, destructive, negative, intrusive thoughts need hope. Lots of it. Daily. Hourly. I know I did. And still do.

In March 2006, I had just finished trying the 23rd combination of mood stabilizers and antidepressants and I still wanted to die. That’s not to mention all the psychotherapy, mindful meditation, light therapy, rigorous exercise, yoga, fish oil, and other techniques I was trying. When my doctor threw out DePaulo’s numbers I did not believe them. However, about two months later, under her care, I was miraculously able to experience a day without any death thoughts. Nada.

The last 18 months have been somewhat of a rerun. I never fully recovered from a crash in August 2011, despite my wholehearted attempts at mindfulness and different kinds of therapy, 10 or so medication combinations, intense exercise, light therapy, diet changes and supplements. Some days were better than others, but I didn’t go much longer than 15 seconds without fighting a death thought. This ongoing silent battle inside my noggin made it very difficult to accomplish anything other than my necessary responsibilities, let alone open space in my life to have fun.

During the last few months, just as in 2006, I have been running dangerously low on hope.

In fact, I began to research transcranial magnetic stimulation, a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of depression. That and electroconvulsive therapy are the last-ditch efforts for those of us checking off double digits of medication combinations and every kind of alternative therapy out there. I was even mapping out my schedule as to how I would spend my morning for two and half months at Johns Hopkins Hospital and how I would explain this to my manager at work.

“Before we go there, let’s try one more combination,” my doctor recommended.

Sure. Yeah. Whatever. Like that’s going to make a difference.

I was wrong. It took the 11th or 14th, or whatever number combination it is, to give my tired brain a respite from the death dialogue, and the stamina I needed to push me into the real world again … so that I can practice mindful meditation in a way that doesn’t make me feel demoralized, or swim in the morning without having to hold back tears, or pursue a passion such as reaching out to those with depression — all of which are important facets to my recovery.

The 80-in-80 aren’t exactly statistics that you’ll hear promised in an ad for an antidepressant, but those numbers sure are chock-full of hope for this depressive. I hope they are for you too, and encourage you to keep on keeping on until you can keep on without quite as much effort.

If you’re taking non-steroidal anti-inflammatory drugs (NSAIDs), you may be less likely to experience the beneficial effects of the most commonly prescribed classes of antidepressants, SSRIs (such as Paxil, Zoloft and Prozac).

NSAIDs include ibuprofin (such as Advil, Motrin, and Midol), naproxen sodium (such as Aleve) and good ole aspirin.

According to an article appearing in the recently published The Carlat Psychiatry Report, that was the surprising conclusion of a paper published last year (Warnerschmidt Jl et al, Proc Natl Acad Sci USA 2011;108:9262–9267), and a newly released report reaches a similar conclusion.

Here’s the report:

Using the electronic medical record of a large HMO, investigators identified 1,528 depressed patients who either achieved remission or who remained treatment-resistant after two or more antidepressant trials. Of these, 1,245 (81%) received at least one prescription of an NSAID or NSAID-like medication during their treatment period. Consistent with the earlier report, depressed patients who received NSAIDs were more likely to be treatment-resistant (odds ratio 1.55, with 95% confidence interval 1.21-2.00).

The investigators attempted to factor out other medical problems. After doing so, the odds ratio remained elevated but was not statistically significant (or=1.17, 95% CI 0.83-1.64).

But then the investigators looked more specifically at the type of NSAIDs used. They found that cyclooxygenase-2 (COX-2) inhibitors — drugs like celecoxib (Celebrex) — and salicylates (aspirin) were not associated with treatment resistance, whereas “pure” NSAIDs were.

Thus, NSAIDs alone (drugs like ibuprofen and naproxen) correlate with treatment resistance, while other NSAID-like drugs do not. This result remained significant even when adjusting for medical comorbidities.

The investigators also performed their analysis on the 1,546 subjects in STAR*D (a large, multicenter antidepressant trial in which all subjects received citalopram in phase I) and found a strikingly similar response: NSAIDs were more highly associated with treatment resistance (or=1.23, 95%CI 1.06-1.44). The risk of treatment resistance was particularly high when coX-2 inhibitors and salicylates were removed, and remained high after controlling for medical problems (OR=1.26, 95%CI 1.02-1.55).

TCPR also notes some problems with the recently published research. For instance, it isn’t based upon a randomized population, doesn’t take into account all possible confounding variables, and didn’t look at the dose-response effect of the relationship. “Nonetheless,” notes TCPR, “its main conclusion is worth considering: patients taking NSAIDs may respond more poorly to antidepressants (Gallagher pJ et al, Am J Psychiatry 2012;169(10):1065–1072).

It concludes:

TCPR’s Take: Should you ask your patients to stop NSAIDs when you prescribe an SSRI? Probably not—and that would be impractical anyway.

But the take-home message seems to be that inflammation and medical illness are linked to depression in ways we are just beginning to understand.

Authors of the earlier paper, for instance, hypothesized that the expression of a certain intracellular protein (called p11) underlies antidepressant response and is enhanced by certain cytokines, while other research holds that inflammation and elevated cytokines are responsible for depression. Clearly more research is needed to tease out these relationships.

Based upon an article by Glen Spielmans, PhD for The Carlat Psychiatry Report.

It turns out, though, that conventional wisdom is largely wrong. Most infertile women who are taking popular antidepressants — such as Prozac, Paxil or Celexa — would help their unborn child by discontinuing the medication. With one exception — those women who are suffering from a severe depression (versus mild or moderate depression).

Why? Those women taking antidepressants nearly double the risk of a miscarriage if they stay on them during their pregnancy.

Researchers from Beth Israel Deaconess Medical Center, Tufts Medical Center and MetroWest Medical Center conducted an extensive literature review to determine what the impact of taking antidepressants was on an infertile woman’s and baby’s health.

It turns out that, except for severe depression, most moms would probably benefit from discontinuing their antidepressant medication during their pregnancy.

As the researchers note, “there is no evidence of benefit, no evidence that these drugs lead to better outcomes for moms and babies.”

Whether antidepressants have any long-term mental health effects on children exposed in utero remains an unanswered question. Nearly a third of newborns born to mothers who took selective serotonin reuptake inhibitors develop a condition called “newborn behavioral syndrome” that causes jitteriness, feeding problems, and inconsolable crying during the first few days or weeks after birth. In some cases, babies develop severe breathing difficulties and require a breathing tube.

“Newborn behavioral syndrome is very rare in babies who aren’t exposed to these drugs,” said Urato; it usually resolves on its own after a short period of time.

Keep in mind, these recommendations are only for women who have mild or moderate clinical depression, not severe depression. And the study specifically looked at only infertile women, who may be undergoing infertility treatment in order to get pregnant (which is not most moms).

Nobody should ever discontinue any prescribed medication without first consulting with their doctor (including antidepressants).

If you’re a pregnant mom taking an antidepressant and have concerns raised by this newest research, please, talk to your doctor. Many effective treatment alternatives exist, such as cognitive-behavioral therapy (CBT).

And of course, untreated depression in a mom is a serious issue that shouldn’t be taken lightly. While nobody is recommending moms go off of an antidepressant medication while pregnant, it is a frank discussion one should have with one’s doctor when one gets pregnant.

Read our writeup: Study Cautions Against SSRI Antidepressants During, Before Pregnancy

Read the full Globe article: Antidepressant risks during pregnancy lead to tough treatment decisions – Health & wellness

The Graedons became so concerned that they commissioned an independent lab analysis of the generic version of Wellbutrin manufactured by Impax Lab and Teva Pharmaceuticals in 2007. This report found that the generic version of Wellbutrin simply wasn’t equivalent to the brand-name version.

In April 2008, the FDA reviewed their existing studies, and concluded they were the same. The FDA did not review the independent analysis, or any actual data on the 300 mg version of the product (you know, the one people were actually complaining about).

Here it is more than four years later, and the U.S. Food and Drug Administration (FDA) finally agrees with the independent analysis, the Graedons, and the hundreds of people who’ve complained about the efficacy of Budeprion XL.

How many thousands of people took generic Wellbutrin with little positive antidepressant effects over the past 5 years only to be hornswaggled, not only by pharmaceutical companies, but by the very government agency empowered to police them?

To show you how screwed up the FDA process is in regards to this dangerous situation, read this paragraph from the FDA news release:

The Impax/Teva product, Budeprion XL 300 mg, was approved in December 2006. Soon after, FDA began to receive reports that patients who were switched from Wellbutrin XL 300 mg to its generic counterparts were experiencing reduced efficacy. FDA analyzed those reports and concluded that the complaints appeared to be linked to the Impax/Teva product.

FDA therefore asked Impax/Teva to conduct a study directly on its 300 mg extended-release product to compare its bioequivalence to Wellbutrin XL 300 mg. FDA asked that the study include patients who had reported lack of efficacy after switching from Wellbutrin XL 300 mg to Budeprion XL 300 mg. Impax/Teva began the study, but terminated it in late 2011, reporting that, despite efforts to enroll patients, Impax/Teva was unable to recruit a significant number of affected patients to generate the necessary data.

So way back in 2006 — six years ago! — the FDA had reports that something was amiss with this drug. It wasn’t working. Patients weren’t getting better on it.

They waited. And waited. And waited some more while the drug company was tasked with conducting one, single, simple study. Five years after the FDA told the company to do the study, the company said, “Nah, we can’t do it. It’s too hard.”

In 2008, the FDA — in an effort to cover its own ass — simply reiterated how it tests generic drugs. At the time, they didn’t require drug manufacturers to test higher doses independently, so they were just going off of the generic data for the 150 mg version of these drugs. They apparently failed to even take a look at the independent analysis commissioned by the Graedons and conducted by ConsuemrLab.com. Doh!

Apparently being deaf, dumb and blind, the FDA decided instead to commission its own study in 2010 (three years after already having the data showing these drugs were not bio-equivalent). Why? Because the patient reports kept coming in despite the FDA’s and Teva’s reassurances that these drugs were the same. (I imagine them saying, “Dumb patients! What do they know?”)

In 2010, in light of the public health interest in obtaining bioequivalence data, FDA decided to sponsor a bioequivalence study comparing Budeprion XL 300 mg to Wellbutrin XL 300 mg. This study was conducted in 24 healthy adult volunteers and was designed to measure both the rate and the extent of release of bupropion into the blood. The results of this study became available in August 2012, and show that Budeprion XL 300 mg tablets fail to release bupropion into the blood at the same rate and to the same extent as Wellbutrin XL 300 mg.

An astounding amount of time passes once again. I’m not sure why it takes nearly 2 years to run a small study of only 24 patients, but hey, I guess since we’re only talking about people’s lives here, no hurry. Thanks FDA!

Five years ago, the FDA knew these drugs were not bio-equivalent, despite its cursory ass-covering 2008 review. During those 5 years, Teva was allowed to continue marketing and selling Budeprion XL 300. How many people died¹ while taking an ineffective antidepressant during those 5 years? Why it took 5 additional years — making thousands of U.S. citizens suffer — isn’t answered in the news release.

And I suspect it never will be.

Read the FDA Alert: FDA Update: Budeprion XL 300 mg Not Therapeutically Equivalent to Wellbutrin XL 300 mg

Read the blog entry over at the People’s Pharmacy: Patients Vindicated! Generic Wellbutrin (Budeprion XL 300) Withdrawn

1. for instance, by taking their own lives because the depressive symptoms were still just too much?

In his new book, Depression: A Guide for the Newly Diagnosed, clinical psychologist Lee Coleman, Ph.D, ABPP, includes a valuable chapter on how to take care of yourself after a depressive episode. Coleman also serves as the assistant director and director of training at the California Institute of Technology’s student counseling center.

Below you’ll find four helpful tips for caring for yourself after an episode of depression.

1. Continue your treatment.

Coleman stresses the importance of continuing your treatment for at least a few months after your depressive episode is over.

He writes, “The window of six to nine months after a depressive episode is particularly critical, and to be on the safe side I often encourage depressed clients to consider the first year after an episode to be a time of heightened risk for relapse and recurrence.”

(Relapse means having another depressive episode within six months of the first one; recurrence means having another episode after six months.)

Research shows that continuing your treatment can reduce both. He also suggests talking to your treatment providers about how you can prevent relapse.

Interpersonal psychotherapy and cognitive behavioral therapy may be helpful in reducing relapse, he writes. Psychotherapy after an episode is valuable because it can help you cope effectively with stress and build resilience.

Also, if you’re taking an antidepressant, don’t stop abruptly. Always talk to your doctor first about discontinuing medication because stopping cold turkey, as Coleman explains, can have serious side effects.

2. Seek help sooner rather than later.

If you start experiencing symptoms of depression again, don’t wait to get help until you meet full criteria for the disorder, Coleman writes.

He encourages readers to think about the early signs of your depression, which can clue you in on what to look out for. Pay attention “to the number of symptoms, their severity and duration, and their effect on your life.”

This doesn’t mean that you need to fixate or hyper-focus on how you’re feeling. Everyone has a bad day. As he put it, “Just have a low threshold for resuming treatment.”

3. Don’t isolate yourself.

Maintaining positive relationships is important. Coleman cites one study that found that just being part of a sports team protected some individuals from depression.

4. Practice self-care.

“When you’re recovering from depression, it’s especially important for you to have some routine in your life,” Coleman writes.

He clarifies that this doesn’t mean leading a boring life. It simply means taking good care of yourself, which includes getting enough sleep, eating nutritious foods and exercising. (Here’s one study on the importance of moderate exercise for reducing relapse.)

If you’d like to learn more about Coleman’s book, check out our review on Psych Central.

How about you?
What has helped you in caring for yourself after a depressive episode? 

You might want to check out a drug more popularly known among the club scene and all-night dance parties than for the treatment of depression.

As we reported last month, researchers are taking a second look at ketamine — also known as Special K in the club scene — to help with depression.¹ It appears it has the potential to be faster-acting than traditional antidepressants, which may make it a new treatment option for people who are depressed and are suicidal or in crisis.

Ketamine is already approved for certain medical uses, such as a human anesthetic, but its use is tightly controlled by the U.S. Drug Enforcement Administration because of its potential for abuse. Now a number of pharmaceutical companies are investigating its use in the treatment of depression with active research trials around the world.

Bloomberg News has the story:

Ketamine may help patients who don’t respond to conventional antidepressants, such as Cymbalta or Lexapro, which don’t work on about a third of those who try them, says Alana Simorellis, an analyst with Decision Resources Inc. in Waltham, Massachusetts. It may also benefit people who need urgent relief from suicidal tendencies, so long as the drug is given under the supervision of doctors in a hospital, she said.

“There is really no medical intervention for acute suicidality, which is a medical and psychiatric emergency,” said Mount Sinai’s Murrough, who is running a trial to investigate the drug’s potential to prevent suicide. “It’s a huge unmet need.”

Besides Sydney and New York, ketamine is being investigated for depression at sites in Boston, Houston and Miami, as well as Changzhou, China; Grenoble, France; Geneva, Switzerland; and Aberdeen, Scotland, according to data compiled by Bloomberg.

Lisa Monteggia, Ph.D., associate professor of psychiatry at University of Texas, noted, “Ketamine produces a very sharp increase that immediately relieves depression.” Monteggia was the lead author on a study published in last month’s Nature about ketamine’s use for depression.

“Ketamine produces a fast-acting antidepressant effect, and we hope our investigation provides critical information to treat depression effectively sooner.” Current antidepressants can take anywhere from 6 to 8 weeks to become fully effective, and most only relieve some — but not all — symptoms of depression.

But this is hardly new news.

For instance, back in 2007 — 5 years ago — there was a study demonstrating that ketamine relieves depression in hours.²

Of course, the real question will be how to offer a new formulation of ketamine that will allow for more widespread use, while significantly reducing the use of abuse or addition.

If additional research confirms these findings and pharmaceutical companies can crack the abuse issue, ketamine may find a new and more popular use — as a fast-acting antidepressant used to help people where traditional antidepressants have been found ineffective.

Read the full article: Special K for Depression Renews Hope in Hallucinogens

1. We also noted nearly 2 years ago that ketamine also provides relief to bipolar patients.
2. In a study that was published in Biological Psychiatry, June 23, 2007.

Medications used to treat mental disorders continue to enjoy the best sales they’ve had ever. Meanwhile, psychotherapy usage continues to decline.

We started tracking the top 25 psychiatric medications prescribed in the U.S. back in 2005, with the help of IMS Health and their innovative Xponent service, which tracks the vast majority of prescriptions dispensed in the U.S.

The top 5 are below, while the rest of the list follows.

1. Xanax (alprazolam) – 47,792,000
2. Celexa (citalopram) – 37,728,000
3. Zoloft (sertraline) – 37,208,000
4. Ativan (lorazepam) – 27,172,000
5. Prozac (fluoxetine HCL) – 24,507,000

To put the percent changes below into perspective, the U.S. total population rose approximately 1.6 percent from 2009 to 2011. That suggests that anything above 1.6 percent change was driven by other factors — more people seeking treatment, more pharmaceutical advertising and marketing, or some other factor.

The biggest movers and shakers on the list were Celexa — moving up 15 spots to grab the second most-prescribed psychiatric drug in 2011 — and Wellbutrin XL, moving from 22 to 13.

Drugs used to treat attention deficit hyperactivity disorder (ADHD) — generic amphetamine salts and methylphenidate — enjoyed big gains as well. The rise of generics is not surprising, since once a medication goes off-patent, it becomes cheaper to purchase. Cheaper meds makes them available to more people who can now afford them.

Check out the Top 25 Psychiatric Medication Prescriptions for 2011 now.

A row of split and shaved Paxil fragments, lined up in descending size, that I took near the end of my taper.

You’ve been taking an antidepressant. It’s been years, hasn’t it?

Perhaps you don’t even clearly remember a time before your days were marked by the morning ritual of swallowing an SSRI.

And now, with the help of your doctor, you’d like to get off the drugs & attack your original condition from another angle. You want to see what life is like without meds. You want to see if, over the years, you’ve developed enough coping skills to manage your depression or anxiety without a daily pill.

So, where do you begin?

Right here.

Before you and your doctor make your first dosage cut, watch this video. It comes from the heart. Back in the mid-2000′s, I tried (and failed) to wean myself off of Paxil twice. (The third time was the charm, but it still wasn’t easy by any means.)

I learned a thing or two from the whole ordeal — and I want to share those lessons with you today.

Have you ever withdrawn from an SSRI antidepressant? If so, does your experience differ from mine? What would you recommend to someone who is trying to withdraw from their meds?

(You can find the original post that inspired this video here.)

Likewise, you are not the only person with an anxiety disorder.

But it can sure feel that way sometimes, eh? Especially on days when everyone else at the party is acting super sociable, but you’re slunked (is that a word?) down in a corner and too dizzy to talk to anyone.

It’s easy to feel alone on days when everyone else seems to be gathering their groceries from the store shelves just fine, but you’re still hovering in the breezeway, leaning on your cart, and trying to muster up the courage to walk inside.

And it’s easy to feel alone at work, too. Everyone else can pay attention to the corporate PowerPoint presentation in the conference room, but you’re sitting next to the closed door, thinking about how far you are from the office restroom, and flexing your leg muscles for a quick escape.

Every time we say “I am alone!” we are lying.

We are not alone in our struggles…and I made a video, just for you, to prove it:

Links:

• Panic! A Blog About Panic, Anxiety, Depression, and Related Topics
• She Gets a Little Nervous
• Prozac Withdrawal
• Panic About Anxiety
• Angst in Anxiety
• Anxiety & OCD Exposed