NSG 502 Chose a medication discussed from the Anti-psychotic or Mood Stabilizer Power Points

NSG 502 Chose a medication discussed from the Anti-psychotic or Mood Stabilizer Power Points

NSG 502 Chose a medication discussed from the Anti-psychotic or Mood Stabilizer Power Points

At the psychiatric facility I work at, I have seen an increase in patients being treated with Lamotrigine (generically commonly known as Lamictal). I have heard prescribers discussing it’s effectiveness in specifically treating the depressive aspect of bipolar. Our lecture mentioned that Lamictal “treats from below” (depression) as opposed to “treating from above” (mania). I have learned about the risk of throwing a patient into a manic episode if using an antidepressant as monotherapy to treat the depression associated with bipolar, therefore I was curious about whether Lamictal could be an alternative to combination therapy for bipolar depression and decided to investigate this drug further.

The kindling of neurons in the frontal lobe is theorized to be the cause of seizures. Similarly, the excess firing of neurons in the limbic system is theorized to cause mood disorders. Lamotrigine is a mood stabilizer and anticonvulsant with FDA approval for maintenance treatment of bipolar 1 disorder. Lamotrigine is also FDA approved to treat partial seizures, generalized seizures of lennox-gastaut syndrome, and primary tonic-clonic seizures. Off label it is used for bipolar depression, and although it is considered and prescribed by many providers, it is not yet FDA approved for bipolar depression. It is also used off label for bipolar mania, psychosis, schizophrenia, neuropathic pain, and major depressive disorder (Stahl, 2017). Lamotrigine is thought to prevent seizures and stabilize mood by blocking voltage-sensitive sodium channels and by inhibiting the release of glutamate and asparate. It is a Glu-CB or glutamate, voltage-gated sodium channel blocker, and is considered an antagonist of voltage sensitive sodium channels (Stahl, 2017).

Lamotrigine is absorbed rapidly and completely and its distribution is not affected by food. It has 100% bioavailability, and is 55% protein bound. It is metabolized in the liver primarily through conjugation, rather than through the CYP450 enzyme system, however there is some UGT1A4 & 2B7 enzyme involvement (Procyshyn & Butler, 2017). It has an inactive metabolite and induces it’s own metabolism. In acute use lamotrigine has a 33 hour half life, while it’s half like is 26 hours with chronic use. Lamotrigine is renally excreted (Procyshyn & Butler, 2017).

Lamotrigine has a uniquely high tolerability profile in comparison to other antidepressant mood stabilizers. Side effects include dizziness, ataxia, blurred or double vision, sedation, headache, tremor, insomnia, poor coordination, and fatigue. Nausea, vomiting, dyspepsia, and rhinitis may also occur. The majority of side effects are considered central nervous system side effects and are caused by the excessive actions occurring at voltage-sensitive sodium channels (Stahl, 2017).

Lab tests are not typically utilized during Lamotrigine therapy as the value of monitoring plasma concentrations has not been established. Lamotrigine binds to melanin containing tissues, therefore ophthalmological checks may be advised (Stahl, 2017). The most important aspect of patient monitoring and education is that of toxic epidermal necrolysis described below.

Lamotrigine comes with a black box warning for a severe life threatening rash called Stevens Johnson syndrome (toxic epidermal necrolysis). This side effect is considered an allergic reaction and can be minimized by very slow titration upon initiation, educating and monitoring for symptoms, and avoiding drug interactions that raise levels such as valproate (Stahl, 2013). In order to safely monitor for this life threatening rash and respond appropriately, providers must educate patients to immediately contact them should a rash appear. Rashes that are widespread with involvement of neck, upper trunk, and involvement of lips, eyes and mouth with associated symptoms of fever, malaise, pharyngitis, anorexia or lymphadenopathy are most concerning. Laboratory tests for complete blood count, liver function, urea, and creatinine should be collected if there is concern of Stevens Johnson syndrome. Lamictal should be discontinued in this event, and hospitalization may be required (Stahl, 2017).

 

References:

Ric Procyshyn, Kalyna Bzchlibnyk-Butler, J. Joel Jeffries. (2017). Clinical Handbook of        Psychotropic Drugs; 22nd edition. Ashland: Hogrefe Publishing.

Stahl, S. M. (2017). Stahl’s essential Psychopharmacology, Prescriber’s guide (6th ed.). Cambridge University Press.

Stephen M. Stahl, (2013). Stahl’s Essential Psychopharmacology Neuroscientific Basis and Practical Applications; 4th Edition. New York: Cambridge University Press.

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I see lamotrigine prescribed quite frequently as well for bipolar maintenance due to tolerability and less risk of weight gain. I have seen a lamotrigine rash before in a patient who was on 25mg per day for two weeks, then appeared at the 50mg dose two days after initiating. Her rash was systemic and pruritic, but fortunately did not progress to Steven Johnson syndrome (SJS) or toxic epidermal necrolysis as the medication was stopped. Her rash resolved within two weeks of discontinuation of lamotrigine.

According to Kverno, Beauvois, and Dudley-Brown (2018), lamotrigine rashes can occur as soon as five days and as

NSG 502 Chose a medication discussed from the Anti-psychotic or Mood Stabilizer Power Points
NSG 502 Chose a medication discussed from the Anti-psychotic or Mood Stabilizer Power Points

late as eight weeks after starting treatment. Interestingly, the aromatic ring of some anti-epileptics, including lamotrigine and carbamazepine, is thought to contribute to hypersensitivity skin reactions (Kverno et al., 2018). It is important to note that if adding Depakote to lamotrigine, it can increase lamotrigine levels and therefore increase the risk of rash (Stahl, 2020). According to Stahl (2020), a slow titration can reduce the risk of rash by starting at 25mg per day for two weeks, then increasing to 50 mg per day at week three, increasing to 100mg per day at week five, and at week six an increase to 200 mg (Stahl, 2020). Finally, if a patient stops lamotrigine, the provider must evaluate for how long they have been off the medication (Stahl, 2020). According to Stahl (2020), lamotrigine should be restarted at an initial titration dose of 25mg per day if the patient has been off the medication for longer five days. Kverno et al. (2018) note the importance of stopping lamotrigine for a rash due to risks of progression to more life-threatening rashes such as SJS. Although the percentage of individuals who develop a rash with lamotrigine are low, careful titration and knowledge of drug interactions can reduce this risk (Stahl, 2020).

 

Kverno, K., Beauvois, L., & Dudley-Brown, S. (2018). Lamotrigine rash: benign allergy or severe adverse reaction? Nurse Practitioner43(3), 48–51. https://doi-org.rivier.idm.oclc.org/10.1097/01.NPR.0000530211.32278.96.

Stahl, S.M. (2020). Stahl’s Essential Psychopharmacology Prescriber’s             Guide (7th Ed.).   Cambridge University Press: New York, NY.  ISBN-10: 1108926010.

I find lamotrigine particularly useful for its ability to “treat from below” as you mentioned in your post. Most, if not all, of our known mood stabilizers treat from above which only solves half of the problem in the case of bipolar disorder. An interesting article I read compared the efficacy of Lithium, lamotrigine, and valproate acid. Researchers concluded that in patients with Bipolar Disorder type II, a comorbid condition, and a history of mixed episodes were more likely to respond better to lamotrigine than the others (Woo et al., 2020). Though Lithium is still considered the gold standard of bipolar disorder treatment, I am curious to learn more about these newer therapies and how they can be applied in practice using evidence-based guidance.

Stahl (2021) names Lithium and atypical antipsychotics as appropriate augmenting agents for partial response or treatment resistance to lamotrigine. Indeed, I have witnessed this method of prescribing many times in practice. Recently I have learned just how slow lamotrigine needs to be titrated. Generally, patients are started on a 25mg dose and remain on that dose for 1-2 weeks before safely being titrated to a 50mg dose (Aiken, 2020). This slow titration schedule continues until the target dose of 200mg a day is reached, or a therapeutic response is observed and maintained (Stahl, 2021). Furthermore, due to the possibility of Steven’s Johnson Syndrome, several parameters should be followed prior to beginning a patient on a regimen with lamotrigine. Some of these include avoiding the start of lamotrigine within two weeks of an inflammatory illness, vaccination, or rash as well as avoiding common triggers to inflammation (Aiken, 2020). As you included, monitoring for Steven’s Johnson Syndrome is critical while on this medication as this condition may be life-threatening if not treated immediately.

You did an excellent job on your post and provided extensive information on the pharmacology of Lamotrigine.

References

Chris Aiken, M. D. (2020, November 16). How to minimize Lamotrigine’s adverse effects. Psychiatric Times. Retrieved October 12, 2021, from https://www.psychiatrictimes.com/view/how-minimize-lamotrigines-adverse-effects.

Stahl, S. M., Grady, M. M., & Muntner, N. (2021). Stahl’s essential psychopharmacology: Prescriber’s Guide. Cambridge University Press.

Woo, Y. S., Yoon, B.-H., Song, J.-H., Seo, J. S., Nam, B., Lee, K., Lee, J., Jung, Y.-E., Kim, M.-D., Lee, J. G., Wang, S.-M., Kwon, Y.-J., & Bahk, W.-M. (2020). Clinical correlates associated with the long-term response of bipolar disorder patients to lithium, valproate or lamotrigine: A retrospective study. PLOS ONE, 15(1). https://doi.org/10.1371/journal.pone.0227217