Lamictal (lamotrigine) for Bipolar: Prophylactic or Prayer?

QuestionYou may have heard of the drug Lamictal or lamotrigine (generic name) being used to treat various mental health issues, including bipolar. For a little over a decade, lamotrigine has been touted as a “mood stabilizer,” not unlike the medication lithium. However, a true mood stabilizer is a medication that—on its own—prevents episodes of mania or depression. Some clinical trials suggest that lamotrigine can prevent depressive episodes, but nothing like the clinical research showing lithium’s efficacy.

Lamotrigine and lithium are supposed to sustain a window or metaphorical room to contain symptoms and thus prevent mood episodes. It has been understood that lithium acts as a ceiling for preventing manic symptoms. Lamotrigine is the floor of that room, so the person does not fall into a basement-dwelling depression. Is this metaphor remotely accurate? Or are we dealing with a 21st-century version of the direct-to-consumer marketing strategy built around the “chemical imbalance theory”? What is the whole story behind lamotrigine?

Lamotrigine is an atypical anticonvulsant medication. The initial purpose of the drug was the treatment of seizures, and it has since been applied to various mental health issues. Clinical trials began in 1984 using lamotrigine as both a monotherapy and an adjunct treatment for conditions such as epilepsy. It has been understood that lamotrigine binds to receptors in the brain that inhibit “excitatory” neurotransmitters such as glutamate. Lamotrigine acts to calm these neural firings in the brain. According to Leach et al. (1991), lamotrigine does this with fewer neurological side effects related to motor functioning (e.g., ataxia), learning declines, or working memory issues compared with other antiepileptic drugs (e.g., Tegretol, Dilantin). The most common side effect of lamotrigine is headache (about 25%), but others include dizziness, drowsiness, tremor, and nausea.

More importantly, within the first two months of lamotrigine treatment some individuals develop skin rash. Because of the risk of rash development, the medication is titrated up (usually 25 milligrams per day/week) very slowly. The higher the dosage—especially over short periods of time—the more likely a skin rash will break out. Although rare (3% to 5%), these rashes can require hospitalization and immediate discontinuation of the drug. Stopping the medication and then quickly returning to the previous amount can induce these rashes as well. Based on some clinical trials, one out of 300 individuals prescribed lamotrigine develops more serious and perhaps life-threatening rashes such as Stevens-Johnson syndrome.

In 1994, the Food and Drug Administration (FDA) approved lamotrigine for marketing in the United States as an anticonvulsant medication (patented by Glaxo Wellcome). By the end of the 20th century, studies commenced with small sample sizes for the treatment of bipolar via lamotrigine. Specifically, findings were gathered for the treatment of “rapid cycling” moods and the depressive component of bipolar. Frequent recipients were those with “refractory bipolar” or individuals with bipolar who had not responded positively to other medications or were intolerant of previous psychotropic interventions.

The medication began to show slight improvements for individuals with bipolar in terms of preventing depressive episodes. Calabrese et al. (2003) found for individuals who initially presented with manic symptoms, lamotrigine had a clinically significant effect at preventing a depressive episode over a one-year period versus placebo and lithium intervention. There was no significant difference for reducing manic episodes compared to placebo. The methods of these types of trials (i.e., “relapse prevention design”) have been scrutinized by some who suggest true “mood stabilizers” need to be tested over longer periods with consideration given to enrichment, withdrawal, and polarity effects (see Goodwin et al., 2011).

In the Calabrese et al. (2003) study, superiority of lamotrigine over placebo was modest and there was a sobering “financial disclosure.” Head researchers in the study were involved in advisory boards, received funding from, were employed by and consulted for GlaxoSmithKline, Glaxo Wellcome, Janssen, Eli Lilly, and UCB Pharma, Inc., to name a few. Was there an incentive for a positive trial?

The cautionary lamotrigine tale often omitted is that individuals taking the medication have a potential for the onset of seizures. Functionally, lamotrigine is an anti-seizure medication.

In 2003, these unassertive findings were influential to the FDA approval (it requires only two positive trials over placebo) of lamotrigine for the maintenance treatment of bipolar depression. GlaxoSmithKline was granted a patent on lamotrigine (i.e., brand name Lamictal, and in 2009, Lamictal XR). The drug became one of the bestselling pharmaceuticals in the United States ($2 billion annually) and launched a multibillion-dollar company. It is hard to trust a corporation with so much power, money, and influence over the psychiatric milieu.

In June 2012, GlaxoSmithKline agreed to plead guilty to wide-ranging, federal criminal charges and civil allegations. The $3 billion was the largest settlement by a drug company at the time. Two-thirds of the civil settlement was due in order to resolve civil liabilities under the False Claims Act. They were charged with the unlawful promotion of various drugs—including Lamictal—for off-label, noncovered uses, failure to disclose safety data, and paying kickbacks to physicians to prescribe drugs during periods from the late 1990s through 2007.

For example, GlaxoSmithKline marketed Paxil to children as being non-habit-forming and lacking withdrawal symptoms. The government claims that GlaxoSmithKline published and distributed a journal article that falsely concluded that Paxil had positive results with pediatric use.

Lawsuits claimed that the drug has serious side effects, which GlaxoSmithKline allegedly downplayed in patient information. In 2001, the World Health Organization ranked Paxil as the most difficult antidepressant to withdraw from. One can’t help but wonder if a similar case will eventually surface relative to the practices surrounding Lamictal (i.e., lamotrigine). GlaxoSmithKline has since been forced to implement and start maintaining transparency in its research practices and publication policies.

The cautionary lamotrigine tale often omitted is that individuals taking the medication have a potential for the onset of seizures. Functionally, lamotrigine is an anti-seizure medication. What happens over time is the brain becomes sensitized to the medication. While administering the drug, you are telling your brain, Hey, I don’t want you to have a seizure. Over time, the absence of the drug makes the brain sensitive to overstimulation. The overstimulation of the brain combined with a rapid reduction of the medicine (e.g., forgetting to take a dose or stopping the medication abruptly) can result in tonic (loss of consciousness, body arching, difficulty breathing), clonic (muscle spasms, jerking), or tonic-clonic seizures (formerly known as grand mal seizures).

You don’t need an epileptic history to develop these types of seizures. The result can come solely from the use, discontinuation, and/or an increased tolerance to a dosage of lamotrigine. Anecdotally speaking, few people are informed of this potential adverse event when prescribed the medication. In addition, the off-label use of this medication is increasing for various conditions such as migraines and pain management as well as mental health disturbances (e.g., borderline personality, refractory depression, posttraumatic stress, schizoaffective condition, and depersonalization).

Make no mistake about it: lamotrigine is not an antidepressant and it does not stop manic symptoms. It does not directly alter levels of serotonin. Eliminating the medical jargon, it reduces agitation and anxiety to keep one’s mood stable. The drug keeps the excitement levels turned down or, put another way, decreases electrical activity (think analogically to how stress can induce a seizure for someone with epilepsy).

Lamotrigine will not miraculously lift a weighing depression, nor will it bring one down from the heights of mania. Although it has become heralded as a prophylactic medication or preventive form of treatment for bipolar mood episodes (depressive episodes), it is lithium that remains the gold-standard treatment. At best, lamotrigine is birth control to the gestation of depression, not the plan B (morning-after pill) or abortion of depressive symptoms once conceived.

References:

  1. Biton, V., Bassel, F.S., Naritoku, D., Hammer, A.E., Vuong, A., Caldwell, P.T., & Messenheimer, J.A. (2013). Long-Term Tolerability and Safety of Lamotrigine Extended-Release: Pooled Analysis of Three Clinical Trials. Clinical Drug Investigation (33):359-364.
  2. Calabrese, J.R., Bowden, C.L., McElroy, S.L., Cookson, J., Andersen, J., Keck, P.E., Rhodes, L., Bolden-Watson, C., Zhou, J., & Ascher, J.A. (1999). Spectrum of Activity of Lamotrigine in Treatment-Refractory Bipolar Disorder. American Journal of Psychiatry, 156 (7): 1019-1023.
  3. Carrier, M. (2014). A US Court issues formalistic ruling on reverse-payment settlements after ‘Actavis’ (GlaxoSmithKline / Teva Pharmaceuticals / Louisiana Wholesale Drug Company / King Drug Company). e-Competitions National Competition Laws Bulletin.
  4. Cohen, A.F., Land, G.S., Breimer, B.D., Yuen, W.C., Winton, C., & Peck, A.W. (1987). Lamotrigine, a new anticonvulsant: Pharmacokinetics in normal humans. Clinical Pharmacological Therapy, 42 (5): 535-541.
  5. Doshi, P. (2013). Putting GlaxoSmithKline to the test over paroxetine. BMJ. 1-3 DOI: 10.1136/bmj.f6754
  6. Goodwin, F.K., Whitman, E.A., & Ghaemi, S.N. (2011). Maintenance Treatment Study Designs in Bipolar Disorder: Do They Demonstrate that Atypical Neuroleptics (Antipsychotics) are Mood Stabilizers? CNS Drugs, 25 (10): 819-827.
  7. Guberman, A.H., Besag, F.M.C., Brodie, M.J., Dooley, J.M., Duchowny, M.S., Pellock, J.M., Richens, A., Stern, R.S., & Trevathan, E. (1999). Lamotrigine-Associated Rash: Risk/Benefit Considerations in Adults and Children. Epilepsia, 40 (7): 985-991.
  8. Hirschowitz, J., Kolevzon, A., & Garakani, A. (2010). The Pharmacological Treatment of Bipolar Disorder: The Question of Modern Advances. Harvard Review of Psychiatry, 18 (5): 266-278. DOI: 10.3109/10673229.2010.507042
  9. Johns Hopkins Medicine Neurology and Neurosurgery. Tonic and Clonic Seizures. Retrieved from http://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/epilepsy/seizures/types/tonic-and-clonic-seizures.html
  10. Leach, M.J., Baxter, M.G., & Critchley, M.A.E. (1991). Neurochemical and Behavioral Aspects of Lamotrigine. Raven Press, Ltd., New York. Epilepsia, 32 (2): S4-S8.
  11. Miller, A.A., Wheatley, P., Sawyer, D.A., Baxter, M.G., & Roth, B. (1986). Pharmacological Studies on Lamotrigine, A Novel Potential Antiepileptic Drug: I. Anticonvulsant Profile in Mice and Rats. Raven Press. New York. Epilepsia, 27(5): 483-489.
  12. Moylan, T. (2012). Glaxo To Plead Guilty, Will Pay $3 Billion Stemming From Drug Marketing. LexisNexis Legal Newsroom: “Litigation”. Retrieved from https://perma.cc/ZFN2-QFNS?type=image
  13. Richens, A. (2007). Safety of Lamotrigine. Raven Press, Ltd., New York. Epilepsia, 35 (5): S37-S40.
  14. Roehr, B. (2012). GlaxoSmithKline is fined record $3bn in US. BMJ. Retrieved from http://www.bmj.com/content/345/bmj.e4568

© Copyright 2015 GoodTherapy.org. All rights reserved. Permission to publish granted by Andrew Archer, LICSW, therapist in Mankato, Minnesota

The preceding article was solely written by the author named above. Any views and opinions expressed are not necessarily shared by GoodTherapy.org. Questions or concerns about the preceding article can be directed to the author or posted as a comment below.

  • 18 comments
  • Leave a Comment
  • Hannah

    Hannah

    July 6th, 2015 at 12:02 PM

    But there have to be those who have shown improvement on this medication; otherwise it would not have received approval to be prescribed correct?

  • Frannie

    Frannie

    July 6th, 2015 at 4:00 PM

    If something isn’t broken, like as you say the gold standard which is lithium for treatment of this disorder, then why is there this continual push to do something more, better? I mean, if this works for numerous people, and it is apparent from the widespread support that the drug has that it does, then I would think that maybe you could tweak the dosage and stuff for certain patients, but that this should remain the treatment which is the go to solution.

  • Kackie

    Kackie

    July 6th, 2015 at 7:03 PM

    Personal experience – Lamictal changed my life. It made me into a functional person again. They say it didn’t help mania but before I was taking it I had years of mania and tried different kinds of meds and would stay up 48 hours at a time etc. and that disappeared with Lamictal. I also stopped having such deep depressive episodes as I had before… Before that I had been unable to keep a job, was chronically suicidal and was on my second hospitalization when I was prescribed Lamictal. I had about 6 years of different unsuccessful medication trials in conjunction with therapy prior to this. I then got my Masters in professional counseling and have been therapist for 10 years. I have not worked with multiple clients whose lives have been positively changed by Lamictal. When you take lithium you have to continually get blood testing to check it which is a huge pain and why I would never want to be on it! So, I know they try to point to studies, conspiracies etc. in this article but speaking from personal experience and professional experience I highly disagree.

  • Kackie

    Kackie

    July 6th, 2015 at 8:47 PM

    Ugh – I meant – I HAVE worked with many clients…

  • Kathy

    Kathy

    July 6th, 2015 at 7:10 PM

    In the early 2000s, I was prescribed Lamictal as an “augmentation and mood stabilizer” to my Effexor. I ended up having double vision. When I stopped the Lamictal cold turkey, the double vision went away. In 2009, I was prescribed Trazadone, a drug I had been on before but this time at a much higher dose. I now have permanent double vision. I stopped that medication and the double vision did not go away. I have seen many doctors and I am told that the muscles in my eyes no longer work together. I can no longer wear contacts and have to wear prism glasses only after suffering for 5 years with contact lenses and double vision. I more or less was told I would have to prove I have it and that prisms are very expensive. I now refuse any “newly marketed” drugs that are the latest trend in the pharmaceutical world. I wish they can see that not being honest about all side effects of drugs can affect a person’s quality of their life forever.

  • Lola

    Lola

    July 6th, 2015 at 7:30 PM

    I have been on many different drugs for bipolar. Lamictal odt with pristiq has worked for me for years now. This combo is the only that has actually worked for me!

  • Naomi

    Naomi

    July 6th, 2015 at 7:37 PM

    This is quite scary. I’ve just begun Lamictal. I understand that there are possible side effects however seizures is not one I’m willing to risk

  • Lesliepooh

    Lesliepooh

    July 6th, 2015 at 8:10 PM

    I disagree with this article. It has done wonders in improving motivation and decreasing anhedonia with a Paranoid Schizophrenic and a Major Depression refractory to meds patient, both of whom would rarely get out of bed and come to treatment before the Lamictal was started. The Paranoid Schizophrenic has a much wider range of emotion now!

  • Kent

    Kent

    July 6th, 2015 at 9:59 PM

    Well, last time I worked with a large scale mental health population, Lamictal wasn’t the first go-to medication. It was used for those unfortunate souls who could not use first tier meds for one reason or another.
    All of these meds should be avoided if possible, but thank god they are there for those who really need them. And I’ve seen dozens of people improve with Lamictal.

  • Junior

    Junior

    July 7th, 2015 at 8:08 AM

    What gets me are the sometimes it seems like the potential side effects are actually going to be worse than your original diagnosis! And that goes for so many drugs these days.

  • Andrew Archer, LCSW

    Andrew Archer, LCSW

    July 8th, 2015 at 4:16 PM

    Thanks for all of the comments and personal stories. I think it is great that this discussion is happening. Hannah, I personally know many individuals who have benefited from taking Lamictal for bipolar disorder. However, there seems to be a lack of transparency regarding the specific mechanism for how Lamictal treats mood issues as well as the side effect profile. This lack of information starts at the top (i.e., pharmaceutical industry) and trickles down to the clinicians (e.g., physicians, therapists, etc.) with the result being a consumer who is not informed. Frannie, the only response I have is that lithium is not patentable, so it is harder to fund research for it and/or make a profit selling it. Kackie, the only thing I want to clarify is that blood draws for lithium are more frequent when it is initially being prescribed. However, once a therapeutic dose is established and the person is stable, blood draws are at most, 3-4 times per year. Kathy, I have also heard about issues regarding double-vision, but it doesn’t seem to be talked about enough. Thank you for offering that. Lola, I think that is wonderful that Lamictal has been helpful to you.

  • Andrew Archer, LCSW

    Andrew Archer, LCSW

    July 8th, 2015 at 4:16 PM

    Naomi, I would discuss the issue of potential seizures with your prescriber and follow their instruction. Lesliepooh, I’m not sure what you mean when you say “disagree” with the article. I tried to make this an objective, reference-based article aimed to increase awareness/understanding. Kent, I appreciate your honesty about both the pitfalls and successes. Junior, having all this information about possible negative effects can make it difficult to imagine how helpful a medication can be.

  • jack

    jack

    July 9th, 2015 at 9:19 AM

    I am not very familiar with bipolar disorder as a whole, but I did wonder if these two medications could somehow be used together, one to prevent the manic episodes and one to prevent the depression.

  • Andrew Archer, LCSW

    Andrew Archer, LCSW

    July 9th, 2015 at 2:31 PM

    Jack, clearly you do know a lot about bipolar disorder. Lamictal is often used in tandem with lithium to prevent both manic and depressive episodes. There are no direct drug interactions between lithium and Lamictal. Lamictal is metabolized via the liver whereas lithium filters through the kidneys.

  • Jack

    Jack

    July 13th, 2015 at 2:51 PM

    Thanks Andrew

  • Diane D

    Diane D

    March 27th, 2017 at 9:38 PM

    Thank you for the professional and in depth information in your article. I am glad I found this in my research. There are many reviews on line and most of the people have bi polar. Many people have side effects. My spouse was just prescribed lamotrigine and I do not want him to take it or to even pick it up from the pharmacy. He spoke with his new doctor about being so sad and crying and this was suggested. I do not know what mood swings really means, but he does NOT go a mile a minute for days on end and then crash. He does not get mad and yell. I think his mood is stable. He is more sad and quiet. The seasonal no sun winter depression affects both of us. He is tired and back pain, getting older , 52 now. Worked hard. I do not think a med like this is going to make him happy and peppy and smiling and talking more. He is a quiet, artist type of man. He is not bi polar nor has a condition that causes seisures. Diet and life style changes will help him. He does take celexa, and it works for years. He was able to excel in his career over the past 15 years. Yes, He has been more sad, and crying due to loss of many loved ones and indecisive over the future. This, I think is normal. I thought that he was more quiet lately, and sometimes anxious. He would not plan or talk with me much, a bit more stubborn and not clueing me in on bills and finances (an off and on again thing !) I thought the celexa, was not working and the doc suggests this as all other anti depressants gave him side effects. I do not think he should take this. I think he will be ok. He just started therapy after me bugging him for almost 2 years! and I see him trying more to share his thoughts. He seems interested in the therapy and now that Spring is almost here getting more sun and fresh air will help as well. He goes inward often, and it was worse before talking with the therapist over the past 6 weeks. He is sad. He does cry. He lost a son. Who wouldn’t! 55+ hrs at work. loss of son, some friends and family have passes.. He is also in the age of male andropause. I want him to have his testosterone checked. He is quiet and keeps his thoughts to himself a lot. He does not like to go out, even on weekends, but never has even 10 years ago. Work is a lot of hours and income is tight so we are home bodys. He just won’t plan at all for outings and seems a little lost at times. Natural at our age. He is healthy, gets up every day to a pretty good job, career. It is an easy commute. The company is good and the people are nice. He has pulled away from me a lot and i was concerned he was more depressed, but this drug does not seem to be what he needs. I think people should try life style changes, diet, new hobbies, get out of the house a little, massage, meditation, reading about mindfulness, exercise first before a pill like this. The docs had me try many things , off label, for neuropathy and fibromyalgia. They all made me feel more depressed and tired, slow, dizzy, brain dead, not talkative, still in pain and sad and one made me cry.I couldn’t work or take care of the house before the meds or while on them. Some bad for the kidneys. Ringing in the ears and poor vision. If all those side effects are not depressing enough they try to add an antidepressant to the mix to combat the side effects of the drug for the pain and fatigue. I just do not want him on the doctor/pill roller coaster they did with me when they were trying to help me fix the chronic pain and fatigue. They had me try 7 different drugs over a period of a year so. I never found one that helped me. They all hurt me. Why would they prescribe this to a man who takes celexa, that i thinks helps him but not enough. Maybe this is normal life… he is perhaps just normal, aging, slower, aches and pains, arthritis, low T, sad and quiet, for people, his son, close to him died. Mid life crisis and over worked and underpaid. Does a pill like this make it all ok? I think it will make things worse. Maybe someone can tell me what they think.
    D

  • Andrew Archer, LCSW

    Andrew Archer, LCSW

    March 28th, 2017 at 9:47 AM

    Thanks Diane for sharing your personal understanding. I appreciate your holistic look at lifestyle, diet and other contributing factors (e.g., stress, transitions, loss). Medications often relieve suffering temporarily, but they are rarely ‘magic bullets’. I’m glad your partner has found someone to connect with regarding his issues.

  • Dave

    Dave

    September 2nd, 2018 at 8:41 AM

    I’m bipolar 2 mixed state. This medicine is, by far, the most helpful.

Leave a Comment

By commenting you acknowledge acceptance of GoodTherapy.org's Terms and Conditions of Use.

* Indicates required field.

GoodTherapy uses cookies to personalize content and ads to provide better services for our users and to analyze our traffic. By continuing to use this site you consent to our cookies.