Gwen writes…

My son was diagnosed with bipolar disorder in the 5th grade. He is now about to turn 21. He cuts and he cannot hold a job or finish a class at the local community college.

His bipolar disorder seems to be more depression-based than manic, or maybe the lithium and Abilify he takes helps the mania but doesn’t treat the depression.

Are there any medications recently developed which can help the depression? I know there is a study underway looking at this problem, but I can’t find out much about it. Sam took the initial test and they said that he qualified, but is no longer interested in participating in the research.

I also know that lithium has long-term effects on the kidneys and this concerns me.

Do you have any suggestions as to resources I can tap to help Sam? His doctor doesn’t really seem to care about looking at alternatives. He hasn’t actually attempted suicide yet, so the doctor seems happy with the status quo. I think we can do better, but don’t know where to turn.

Any suggestions you have would be helpful.

Gwen

Dr. Fink answers…

This email raises a number of questions that are common to many families I have worked with over the years:

• This young man’s diagnosis of bipolar disorder was made over 10 years ago, during a time when there was a lot of over-diagnosis of bipolar disorder in children. As Gwen indicates, her son seems to be showing more depression than mania.Studies are now indicating that many children with mood regulation problems – severe rages and chronically irritable mood – are more likely to be diagnosed with depression and/or anxiety as adults, than bipolar disorder.Since I don’t know the details, I can’t comment on this case in particular, but given the complexities of this diagnosis in children and the debates about it, a family in this situation may want to consider a completely fresh evaluation to carefully review the diagnosis and treatment plan.
• The National Institute of Mental Health (NIMH) could be an extremely valuable resource. Many of the best studies about childhood bipolar disorder are being done there. Dr. Ellen Liebenluft is one of the most respected researchers in the field, and her group may be doing studies that could be appropriate in this situation.But even if there isn’t a study that this young man or other young people would fit into, (or if the young person has no interest in participating in the research as Gwen indicates in her letter) I would encourage families to at least seek out a second opinion from a psychiatrist who is well versed in this area – a child psychiatrist who also works with young adults would be most helpful I think.
• Treating depression in bipolar disorder is often the most difficult and challenging component of the disorder – and choosing medications to try can be very tricky. Some of the choices may change if the diagnosis changes and certainly, even if he truly has bipolar, treatment of the depressive symptoms is going to be an important conversation, since he seems to be having trouble functioning because of these symptoms.There are a variety of options – I cannot comment in particular because I haven’t done an evaluation of this young man – but I encourage patients and families to seek out a different perspective if they feel the current doctor is not attending to important symptoms.
• Gwen doesn’t mention if her son is in therapy – but this is also going to be a crucial part of long term treatment/management of the kinds of difficulties he is living with. In particular, if he is self harming, connecting with a therapist or group who are specialty trained in Dialectical Behavioral Therapy (DBT) may be valuable.This is a skills-based model, a subtype of Cognitive Behavioral Therapy (CBT), and has an excellent track record of helping people with long-term difficulties regulate mood and behavior. Getting a young person to engage in treatment may be difficult, but it is certainly an option to explore.
• Families benefit from support from other families living with these issues. NAMI is a terrific organization that provides information, networking, training, and family-to-family emotional support that is incredibly helpful to those living with or caring for people with mental illness. I strongly encourage families to look into this or other support organizations as part of managing mood disorders for the long term.

Photo by Alexander Konovalenko, available under a Creative Commons attribution license.

Recently Paul Greengard PhD published a report in an online journal that strongly suggests that treatment with NSAIDs may reduce the antidepressant activity of SSRIs. Their research is based on the theory that depression is at least partially related to the body’s inflammatory responses. This is called the cytokine hypothesis and is based on observations that some chemicals released as part of inflammation – cytokines – are involved in regulating neurotransmitters such as serotonin.

It has been found that SSRIs increase levels of particular cytokines and a protein known as p11, which is also related to the cytokine theory of depression. NSAIDs abolish those effects of the SSRIs.

This study of the chemistry of SSRIs and NSAIDs helps outline the possible mechanism behind findings in the STAR*D study – a major study of people with depression – that showed NSAID use was associated with poorer response to SSRIs when they were taken with NSAIDs.

The researchers state that based on the combination of clinical and biochemical studies that now show such a strong negative relationship between these two medicines, doctors should carefully consider the risks and benefits of using NSAIDs in patients being treated for depression.

SSRIs include Prozac (fluoxetine), Zoloft (sertraline), Paxil (paroxetine), Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine).

NSAIDs include aspirin, ibuprofen, and celecoxib (Celebrex), to name only a few of the more common NSAIDs.

If you take SSRIs and NSAIDs you should not stop either medicine, but this is something to discuss with your doctor. The article doesn’t specifically mention whether using NSAIDs occasionally for a headache poses a problem, but the study is based on chronic exposure of cells to the anti-inflammatory agent, so I would expect that this is more of a concern for people who are taking NSAIDs regularly for more long-term pain management. Some people, however, don’t realize how often they’re taking medicines for pain – and it’s something to consider if you’re not having a positive response to your antidepressant.

Photo by Pedro Vera, available under a Creative Commons attribution license.

Mindfulness is a meditation therapy that uses self-control techniques to overcome negative thoughts and emotions and achieve a calmer, more focused state of mind – a moment-to-moment awareness with qualities of kindness, curiosity, and acceptance.

Mindfulness was originally an ancient eastern approach to wellbeing that has been found, through recent psychological research, to be a powerful way of managing a range of mental health conditions.

The great thing about mindfulness is that it’s not only a technique you practice now or then, but a way of living your whole life, moment by moment. People who practice mindfulness regularly find they are more focused, calm, and better able to cope with the challenges of life.

Observing thoughts instead of reacting to them

In mindfulness, you learn to see thoughts as just thoughts rather than as facts or situations you must react to. Thoughts commonly come and go in the mind, and if you treat all thoughts as true and assign them all the same level of importance, you’re more prone to feel down in the midst of negative or self-judgmental thoughts and highly elated in the midst of positive thoughts. This rollercoaster ride of emotions and energy often seems to trace the same path as bipolar disorder’s ups and downs.

By practicing mindfulness, you notice that both types of thoughts are just thoughts, and you don’t need to react to them or even give them your full attention. After all, thoughts arise merely out of your perception of reality or are borne out of your own thought process. You’re not required to give them the full status of being true. Mindfulness involves watching thoughts and stepping back from them – like watching clouds passing through the sky. This enables you to become a disinterested observer, and thoughts lose some of their control over your emotions.

Switching modes of mind

Mindfulness also emphasizes learning to switch modes of mind. Normally you operate in “doing mode,” which is all about setting goals and trying to achieve them. Many people get stuck in this mode and never realize they have the option of shifting to “being mode,” which is all about allowing and accepting things just as they are, rather than working hard to change them.

Being mode is particularly helpful in the realm of emotions. If you’re feeling sad and don’t accept it, you can end up fighting to change the experience. This can lead to a deeper feeling of sadness and trigger a negative thought cycle. By being with the experience and mindfully accepting the emotion, you allow the feeling to dissipate in its own time.

Mindfulness-based cognitive therapy (MBCT) for depression

Mindfulness-based cognitive therapy (MBCT) was developed about 10 years ago as a treatment for recurring depression. MBCT teaches participants the skills that enable them to be more aware of their thoughts without judgment, viewing negative (as well as positive and neutral) thoughts as passing mental events rather than as facts. Research found that an eight-week course in MBCT resulted in a 50 percent reduction in depressive relapse (compared to treatment as usual) for those who had three or more previous episodes of depression. As a result, the National Health Service in the UK now recommends MBCT as the treatment of choice for those who have suffered from three or more depressive episodes.

MBCT is now being rapidly researched for a range of different mental health conditions, including bipolar disorder. Preliminary research published in 2008 by Professor Mark Williams, one of the developers of MBCT, has shown promising results. Researchers studied a small randomized group of people with bipolar disorder in remission. They found an immediate reduction in levels of anxiety for the group compared to those who didn’t receive the MBCT training. Also both bipolar and unipolar participants with MBCT had a reduction in symptoms of depression compared to those who didn’t.

Another experiment on MBCT for bipolar was carried out on 2 groups at Oxford University, UK, and 2 groups at the University of Colorado, USA. These were small groups but again results were promising, showing reduction in depressive symptoms and thoughts about suicide, and to a lesser extent, a reduction in anxiety and manic symptoms.

Mindfulness in managing bipolar disorder

Mindfulness looks like a potentially effective way of managing bipolar disorder, especially the depressive pole, which may be the most difficult to treat with medication alone. Mindfulness exercises and meditations are useful for people with bipolar disorder (manic depression) because mindfulness:

• Decreases the relapse rate for depression.
• Reduces stress and anxiety, which contribute significantly to the onset of both mania and depression and may worsen the course of the illness.
• Improves a person’s ability to manage thoughts and feelings and increases awareness of the way the person tends to internalize external stimuli.

Mindfulness exercises include guided body scan meditation, mindful walking, mindfulness of breath, and mindfulness of thoughts and feelings. All of these exercises are on the audio CD that comes with the book Mindfulness For Dummies.

If you’ve had any sort of mindfulness training, please share your experiences and insights.

Learn more about mindfulness

To find out more, you can read my book, Mindfulness For Dummies, which comes with over one hour of guided mindfulness exercises on CD. Order on Amazon.com.

You may also wish to explore the following resources:

• The Mindful Way through Depression by Williams, Teasdale, and Segal, who developed MBCT. Order on Amazon.com.
• To learn MBCT, try searching for “MBCT” online in your local area.
• To take distance learning courses on MBCT via telephone or Skype contact me at shamash@learnmindfulness.co.uk or visit learnmindfulness.co.uk.
• Find me on Facebook at Facebook.com/learnmindfulness
• Find me on Twitter at twitter.com/shamashalidina

References

• “Mindfulness-based Cognitive Therapy (MBCT) in bipolar disorder: Preliminary evaluation of immediate effects on between-episode functioning,” J.M.G. Williams et al., Journal of Affective Disorders, Volume 107, Issue 1, April 2008.
• “A Pilot Study of Mindfulness-Based Cognitive Therapy for Bipolar Disorder,” David J. Miklowitz, et al., International Journal of Cognitive Therapy, Volume 2, Issue 4, December 2009.
• Innovations and Advances in Cognitive Behavioral Therapy edited by Danielle Einstein, Chapter 3, “Mindfulness Meditation and Bipolar Disorder,” by Jillian Ball, Justine Corry, and Philip Mitchell.

Yes.

An accumulating body of evidence supports the notion that non-medical interventions – especially mindfulness – can create changes in the body and brain that help reduce distress and improve brain function in a variety of ways.

Mindfulness

A mental state of heightened awareness, free of distraction, and more conducive to deliberate thought and action.

Some of the most interesting projects have explored the use of mindfulness practices to reduce stress and depression and improve attention. Several fascinating studies have explored the minds of “experts” in meditation – a form of mindfulness – and clearly show they have strong neuro-circuitry in areas of emotional regulation and feelings of compassion.

A recent study in the journal Neuroimage entitled “Impact of Mindfulness-Based Stress Reduction Training on Intrinsic Brain Connectivity” (Kilpatrick et al., 2011 Feb 17) involved a group of healthy women who were trained for eight weeks in mindfulness meditation skills compared to a group that did not participate in the training. Functional MRI studies at the end of the eight weeks showed “increased functional connectivity” between various areas of the brain in the women who studied mindfulness. The training changed the brain in ways thought to relate to how the brain pays attention and how it processes sensory information.

Some studies have examined the effects of cognitive behavioral therapy (CBT) on obsessive compulsive disorder (OCD) that have similarly suggested brain changes that occur in response to therapy and are related to improving symptoms.

Our feelings and behaviors are the results of complex and constantly evolving interactions of our genetic patterns and the environment acting on those patterns. The environment includes all things that affect us – physical and social/emotional stresses are all part of the story. What we need to keep in mind is that the environmental effects on our systems are just as “biological” as any medication or surgical procedure, and they may affect the brain in positive ways as well as negative.

Nurture is nature; our biological makeup evolves as we interact with the world around us. So the work of helping ourselves feel better involves looking at all the possible ways of creating beneficial changes in the nervous system – from medicine to food to exercise to light to various types of therapies and practices such as mindfulness and beyond.

Come back on Thursday to read guest blogger Shamash Alidina’s post, “Using Mindfulness for Bipolar Disorder.” Shamash Alidina is author of Mindfulness For Dummies.”

If you’ve had any sort of mindfulness training, please share your experiences and insights.

Also on Psych Central, ”How to Be Mindful and Have More Positivity,” by Joe Wilner.

Photo by Dierk Schaefer, available under a Creative Commons attribution license.

SSRI’s work by inhibiting the reabsorption of the neurotransmitter serotonin, effectively increasing the level of serotonin in the synapses of the brain – the space between the brain cells (neurons). This reduces the symptoms of depression and anxiety in many people.

While insufficient serotonin may be one cause of depression, researchers are exploring another possible cause – dysregulation of glutamate. Glutamate is the most abundant excitatory neurotransmitter in the body. Riluzole (Rilutek), a prescription drug commonly used to treat Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS), reduces the release of glutamate while increasing its uptake. Some studies have shown that Riluzole is effective in treating acute bipolar depression alone or in combination with other anti-depressants.

Note: Lithium stabilizes the level of glutamate in the brain, and Lamictal (lamotrigine) is a glutamate blocker, which may help explain their antidepressant properties in some patients. However, the effect of glutamate on depression and bipolar depression is not simply a matter of too much or too little – it is a complex set of interactions between glutamate and several types of brain cells. Studies of different parts of the brain have indicated that elevations and low levels of glutamate are both associated with depression.

Perhaps even more important in respect to treating bipolar depression, Riluzole and other medications that target glutamate may have a lower risk of triggering a switch to mania.

Of course, all medications have side effects. Riluzole is no exception. Following are some caveats for Riluzole:

• Possible liver damage, especially in patients already at risk or who drink excessive amounts of alcohol.
• Caffeinated beverages may increase the effect of riluzole.
• Smoking may speed the elimination of riluzole from the body.
• Riluzole must be taken one hour before or two hours after eating, which can make it inconvenient.

Riluzole is not being used in routine clinical practice yet – but in adults with severe, treatment-resistant depression it would be considered a reasonable medication to try. I have not yet used it in my practice, although I do use N-acetyl cysteine – a supplement related to the glutamate systems – for treatment-resistant depression. Look for more and more research and hopefully new treatment options that target glutamate in the near future. For more about N-acetyl cysteine, see my previous post, “Treating Bipolar Depression with an OTC Supplement?”

If you’re a doctor who has prescribed Riluzole or someone who has taken it for depression, please share your experiences and insights.

Photo by FarmStudioField, available under a Creative Commons attribution license.

What drew my attention recently to rejection sensitivity was an article in this month’s edition of the journal Bipolar Disorder based on a study entitled “Pain during depression and relationship to rejection sensitivity” (Ehnvall A, Mitchell PB, Hadzi-Pavlovic D, Malhi GS, Parker G.). These researchers looked into the relationship between severe, treatment-resistant bipolar depression, pain, and rejection sensitivity.

This study found that in people with severe bipolar depression, increased pain sensations – particularly headaches and chest pain – actually occurred much more often in depressed patients who were also experiencing high levels of rejection sensitivity as part of their depressive episode.

When someone is depressed, a common symptom is perceiving that other people don’t like them or are rejecting them. Based on this study, it seems that specific pathways in the brain relate to depression and to these distorted perceptions about other people. Furthermore, when these pathways are disrupted they overlap into pain circuits, triggering physical discomfort, also a common symptom of depression.

What I found most interesting was the premise of the article – that depression, pain, and rejection sensitivity involve similar brain circuits. While I was familiar with the idea of pain and depression sharing similar wiring, I wasn’t familiar with the notion that rejection sensitivity was part of that brain loop.

I looked into another article to help me understand this, a study entitled “Black sheep get the blues: A psychobiological model of social rejection and depression” (George M. Slavich, Aoife O’Donovan, Elissa S. Epel, Margaret E. Kemeny published in Neuroscience and Behavioral Reviews, August 2010). In this study, participants were subjected to conditions that simulated a socially stressful situation, and researchers measured chemicals in their bodies and scanned their brains in an fMRI. Results showed that in the midst of these stressful situations, the human body releases inflammatory chemicals, just like those released after a physical injury, and those chemicals light up parts of the brain related to emotional distress.

The big story for me in these two studies is that researchers continue to identify brain pathways and circuits in bipolar disorder and depression that are clearly disrupted at a neurochemical level, and that we are starting to be able to focus on pathways that are related to specific symptoms of depression.

Ultimately we can use this information to further understand the complex brain processes involved in how people actually experience and express depression and develop more specific and maybe more efficient treatments. In the meantime, it continues to reinforce the scientific understanding of mood disorders and help us educate and advocate with people who still don’t consider mental illness a real physical illness.

Photo by Julie Jordan Scott, available under a Creative Commons attribution license.

The purpose of this study was to look at a specific type of neurotransmitter – glutamate – that is different than any of the transmitters that our current medications target. The question being asked was whether targeting these particular receptors might provide more rapid relief of depressive symptoms specifically in people with bipolar depression. There have been several previous studies showing a rapid, strong antidepressant response to IV-administered Ketamine in people with depression, but this is the first study to look at these receptors in bipolar depression specifically.

The benefits from the Ketamine lasted an average of 6.8 days, and while one patient on Ketamine became manic, so did one patient on placebo. The side effects included some initial periods of dissociation and changes in perception – these effects were brief, and not everyone experienced them.

Ketamine is used recreationally (as the club drug known as Special K) to get these perceptual and dissociative feelings. This is not discussed in the study but is something to be considered if Ketamine is going to be further evaluated as a potential treatment for depression.

The study is valuable because it adds something to our understanding of the neurochemistry of bipolar disorder and possible new treatment approaches. This study isn’t suggesting that intravenous Ketamine be used in a clinical setting to treat bipolar depression, but it is expanding our knowledge of ways to treat it – and in particular – possibly ways to treat depression much more quickly than we do with our currently available medications. There is a lot of active research on the glutamate system and it is likely to be the next big wave of new interventions for depression.

Medications in this group work differently from SSRI’s(including Prozac and Paxil), SSNRI’s(including Effexor and Cymbalta), and Wellbutrin. While MAOI’s have fallen out of favor since the introduction of the newer generation of antidepressants, they remain effective and may be useful alternatives in some cases.

Monoamine Oxidase Inhibitors (MAOI’s)

Monoamine Oxidase Inhibitorsare the earliest antidepressants, developed in the 1950s. They work by preventing the action of an enzyme that breaks down norepinephrine, serotonin, and dopamine, along with a number of related brain chemicals, resulting in an increase in the levels of these chemicals in the brain. MAO inhibitors include the following:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam)

Emsam is a second generation MAOI that has been released in recent years. The other formulations are much older and have fallen out of favor with most prescribers. Emsam is provided as a skin patch that you apply to your arm, torso, or thigh. The medication passes slowly and gradually through your skin into your bloodstream. By absorbing the medication more slowly, patients may be able to avoid some of the dietary restrictions that often accompany MAOI’s (as explained later in this post).

The main benefit of MAOI’s is the fact that they boost the three main neurotransmitters that affect mood – serotonin, norepinephrine, and dopamine. They may work more effectively on “atypical” types of depressions, as well, and can be powerfully effective antidepressants for some people. They actually have a strong track record specifically with bipolar depression that has not responded to other interventions.

The restrictions on their use over the years have been due primarily to the following three reasons:

• The extensive dietary restrictions required for the older MAOI’s.
• The dangerous effects of not following these restrictions.
• The severe and dangerous interactions between MAOI’s and many, many other medications, including all of the SSRI’s and SNRI’s. Switching from an SSRI to an MAOI requires a number of weeks of a washout period, so that SSRI is completely removed from the system before starting the MAOI.

Like all antidepressants, MAOI’s carry a risk of manic switching and of agitation and/or suicidal ideation.

Potential Side Effects

The side-effect profile for MAOI’s dwarfs that of even the tricyclics. Possible side effects include the following:

• Severe interactions with certain foods and many medications, as described in the following section
• Manic switching
• Agitation and suicidal ideation
• Blurred vision
• Constipation
• Decreased sexual function
• Decreased urine output
• Diarrhea
• Dizziness
• Drowsiness, fatigue
• Dry mouth
• Headache
• Increased appetite and weight gain
• Increased sweating
• Lightheadedness, especially when getting up from a lying or sitting position
• Low blood pressure
• Muscle twitching
• Nausea, upset stomach
• Restlessness
• Shakiness and tremor
• Sleep disturbances
• Weakness

Potentially Dangerous Food and Drug Interactions

MAOI’s can have dangerous interactions with certain foods and beverages, which may result in a spike in blood pressure, possibly causing a stroke. If you take medications in this class, you may face some serious dietary restrictions and have to avoid any foods that contain a high concentration of tyramine, including the following:

• Many cheeses
• Pickled foods
• Chocolates
• Certain meats
• Beer and wine (even the alcohol-free or light varieties)
• Certain beans and legumes

Serious interactions may also occur with certain medications or herbal remedies, including…

• Decongestants
• Herbal weight-loss products
• Meperidine (Demerol) and all narcotic pain relievers
• St. John’s wort
• Tramadol (Ultram)
• All other antidepressants especially those that increase serotonin levels in the brain
• Many other medications

Caution: Consult your doctor prior to adding any medications or herbal remedies to your regimen, even commonly used over-the-counter medications. This is true for all medications but especially critical if you are taking an MAOI.

MAOI’s in My Practice

I have not used MAOI’s in my practice for many years. I have not found the need to go to this level of medication given the many other choices available. MAOI’s, at this point in time, are mostly used in academic settings that handle the most complex kinds of mood disorders.

If you’ve taken any MAOI’s for bipolar depression or other conditions or are a doctor who has prescribed any of the older antidepressants in this class, please share your experiences, insights, and observations.

Medications in this group work differently from SSRI’s (including Prozac and Paxil), SSNRI’s (including Effexor and Cymbalta), and Wellbutrin. While tricyclics have fallen out of favor since the introduction of the newer generation of antidepressants, they remain effective and may be useful alternatives in some cases.

Tricyclic Antidepressants

Tricyclics (so called due to a three-ring chemical structure) inhibit the re-absorption (reuptake) of serotonin, norepinephrine, and (to a lesser extent) dopamine, increasing their availability to brain cells. Tricyclics include the following medications:

• Amitriptyline
• Amoxapine
• Desipramine (Norpramin)
• Doxepin (Sinequan)
• Imipramine (Tofranil, Tofranil-PM)
• Nortriptyline (Pamelor)
• Protriptyline (Vivactil)
• Trimipramine (Surmontil)

Tricyclic antidepressants are effective agents for treating depression and many types of anxiety disorders. However, in individuals with bipolar disorder, tricyclics present a risk of manic switching – quite possibly a higher risk than with more recent agents such as SSRI’s. The tricyclics also have some “niche” uses, including treating insomnia, migraine headaches and some chronic pain syndromes, bedwetting, and ADHD.

Potential Side Effects

Tricyclics also affect a number of other brain chemicals, such as histamine, possibly causing many of the side effects attributed to this class of antidepressants, including (in some cases)…

• Manic switching
• Agitation and suicidal ideation
• Drowsiness
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Dizziness
• Impaired sexual functioning
• Increased heart rate
• Disorientation or confusion
• Headache
• Low blood pressure
• Sensitivity to sunlight
• Increased appetite
• Weight gain
• Nausea
• Weakness

Because of this somewhat overwhelming side-effect profile, doctors typically try tricyclics only when other antidepressants, such as Prozac and Cymbalta, are ineffective or not well tolerated.

Important: Tricyclics are generally contraindicated for people with untreated narrow-angle glaucoma, enlarged prostate, or certain types of heart disease (due to a higher risk of heart attack), or heart-rhythm abnormalities. Tricyclics can also affect blood sugar levels, so if you have diabetes, your doctor may instruct you to check your blood sugar levels more often. If you have a history of seizures or thyroid problems, use tricyclics cautiously, if at all.

Tricyclics in My Practice

When I was training in psychiatry, tricyclics were still the most widely used antidepressants, as the SSRI family of medicines was just starting to appear in the US. They were effective and often well tolerated but could have many side effects. People often felt a little druggy and sedated on them, at least for a while. In my current practice, I rarely use tricyclics unless other options have been ineffective or not tolerated. I have a few people on them who benefit from the medication making them feel sleepy. A few of my patients take low doses specifically for sleep.

In the 70′s and 80′s tricyclics were popular alternatives to stimulants for treating ADHD in children. But after a number of reports of sudden death in children on tricyclics, these medications rapidly fell out of favor and are almost never used in children anymore.

A few people I work with are on low dose tricyclics to treat migraine headaches – the neurologists will sometimes use these medicines for headache and other pain-management situations.

Remember: Any antidepressant can take 2-3 weeks or even longer to become fully effective, and it may take several weeks to work up to a therapeutic dose, so your depression may not lift for several weeks. Patience is key. Give the medication a few weeks to become effective and give your body a few weeks to adjust to it. Any negative side effects you experience are likely to fade over time.
Schedule an appointment to follow up with your doctor 3-4 weeks after you start taking the medication, but don’t hesitate to call earlier if you’re concerned about the medication’s effectiveness or any side effects you may be experiencing.

If you’ve taken any tricyclics for bipolar depression or other conditions or are a doctor who has prescribed any of the antidepressants in this class, please share your experiences, insights, and observations.

As a group, the SSRI’s share many of the same potential benefits and potential negative side effects, so we encourage you to read the Prozac post first to get up to speed about general information relating to SSRI’s, including how SSRI’s work and important cautions about using any antidepressant to treat depression in bipolar. In this post, we focus on Luvox’s profile in treating bipolar depression and depression in general.

Potential Benefits

The name brand Luvox is not longer available – it is only available as a generic, fluvoxamine. Luvox CR is newer version, which is a once-a-day product as opposed to the twice-a-day dosing required with generic fluvoxamine.

Luvox has FDA indications for the treatment of Social Anxiety Disorder and OCD (its most common usage). It is approved for the treatment of OCD for children as young as 8 years old.

Luvox may also be useful in treating other anxiety and mood disorders, including the following:

• Unipolar depression
• Bipolar depression
• Post Traumatic Stress Disorder (PTSD)
• Bulimia nervosa
• Generalized Anxiety Disorder (GAD)
• Panic Disorder

Typical Dose

Typical adult doses of Luvox range from 50 mg to 300 mg taken once daily, higher in some cases, same time each day, but follow your prescriber’s recommendations on dose and when to take it.

Potential Side Effects

Like most medications in its class, Luvox can potentially cause any of several negative side effects. The most serious are the following:

• Increased suicidal thoughts in children or teens: Clearly there is an increased risk of suicide and suicidal thinking in people with bipolar and depression as a whole. A large review of studies done on children and adolescents who were treated with antidepressants showed that there was a slight increase in the risk that these children would develop suicidal thoughts, compared to children taking placebo. Even with the increased risk, the rate of this side effect remains very, very low. And the increased risk relates only to suicidal thinking- there have been no reports indicating any increased risk of completed suicides with the medications. These medications are far more likely to decrease the risk of suicide than to increase it. Careful monitoring and communication with the prescriber, especially early on in treatment with SSRI’s, is essential in reducing this risk as much as possible.
• Increased risk of mania: As mentioned earlier in this post, a person with bipolar disorder taking an antidepressant without the protection of a mood stabilizer may be at higher risk of shifting into mania or hypomania. While there is some indication that some antidepressants have less risk of manic switching, the risk seems to be present in all antidepressants. The rate of switching and the actual level of risk is not clear at this time – some researchers suspect it is very high and others feel it is actually much lower than is generally presumed.
• Agitation, increased anxiety, or worsening depression or other paradoxical effects: This is not the same as a true manic switch, and can occur in people with or without bipolar disorder who take SSRI’s. In a small group of people, these medicines seem to irritate the brain wiring rather than soothe it. This appears to be more common in children and adolescents, but can occur in a subset of adults as well. Close monitoring with your prescriber will be important in detecting this.
• Serotonin syndrome: When combined with medicines used to treat migraine headaches known triptans, such as sumatriptan (Imitrex), or other drugs that elevate brain levels of serotonin (including the illegal drug Ecstasy), a life-threatening condition called serotonin syndrome can occur. Symptoms include restlessness, hallucinations, loss of coordination, racing heart, increased body temperature, blood pressure fluctuations, overactive reflexes, diarrhea, nausea, vomiting, coma, and possibly death.
• Persistent pulmonary hypertension of the newborn (PPHN): There are studies showing that babies born to mothers who were taking SSRI’S in the third trimester of pregnancy have an increased likelihood of this condition. Babies born with PPHN have restricted blood flow through their heart and lungs, reducing the supply of oxygen to their bodies. This can make them very ill and increase their risk of death. If you’re pregnant or planning to become pregnant, consult with the doctor who’s managing your medications.

Luvox has a number of interactions with other medications, so it is important to review your entire medication regimen with your physician before starting Luvox or adding another medication while already taking Luvox. There are interactions with the benzodiazepines (tranquilizers), as well as certain sleep medicines and a number of medicines for other health issues.

Other less serious side effects can include the following (Note: Many of these side effects are transient and occur when first taking these medications but do not persist.):

• Sweating
• Sleepiness
• Insomnia
• Nausea
• Diarrhea
• Tremor
• Dry mouth
• Loss of strength
• Headache
• Weight loss or gain
• Dizziness
• Restlessness
• Mania
• Changes in sexual function

Remember: Any antidepressant can take 2-3 weeks or even longer to become fully effective; it may take several weeks to work up to a therapeutic dose. This means that your depression may not lift for several weeks. I often tell patients however they feel in the first two weeks is unlikely to be how they feel in a month – so if they are feeling some early side effects, hold on because they will likely get better. Patience is important in getting these medications to work, but if you have any concerns about how you are feeling, you should contact your doctor. You will most likely have a follow-up visit with your doctor within a month or less of starting the medications; this is a good time frame for checking in to see if benefits have started or if side effects have faded or persisted.

Since Luvox has a childhood indication, I use it frequently in my young patients for OCD and for anxiety disorders. It is less commonly used for depression and bipolar depression – particularly the latter due to the risk of triggering mania or agitation. However, if there is depression along with OCD or other severe anxiety symptoms Luvox can be a powerful tool in the tool box.

The most common potential side effect is sleepiness, so we titrate the dose up fairly slowly, which means it can take longer to work. Also, the interactions with other drugs can make it a more difficult medication to prescribe, particularly in adults with any medical conditions.

For more about Luvox CR (extended-release capsules), visit Solvay Pharmaceuticals’ LuvoxCR page.

If you’ve taken any form of Luvox for bipolar depression or other conditions or are a doctor who has prescribed it, please share your experiences, insights, and observations.