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Lamictal For Treatment Resistant Depression

Who Is A Good Candidate For Esketamine Therapy

Medications for Depression & Bipolar | Robert D. McMullen, MD

Currently, esketamine is approved for people with treatment-resistant depression. That means youve tried at least two other antidepressants and havent experienced remission or at least a 50% improvement in mood.

For people who havent had success with other antidepressants, esketamine gives them the chance to see what its like to not have depression, says Kaplin. It gives them hope that they can feel better with the right treatment.

Esketamine Helps The Brain Form New Connections

Research suggests that untreated depression causes long-term brain damage and is a risk factor for dementia. Studies show that people with depression have up to 20% shrinkage of the hippocampus, a region of the brain critical for memory and learning. But esketamine may counteract the harmful effects of depression.

Animal studies indicate that connections between brain cells diminish under chronic stress, but esketamine reverses these stress-related changes. Esketamine is different than any other antidepressant in that it not only prevents the neurotoxic effects of depression on the brain, but it also seems to have a growth-promoting effect, explains Kaplin.

Esketamine Decreases Suicidal Thoughts

Conventional antidepressants may actually increase suicidal thoughts at the beginning of treatment, especially in children and young adults. Esketamine is the only drug besides lithium, a drug commonly prescribed for bipolar disorder, thats proven to decrease suicidal thoughts, says Kaplin. Although esketamine isnt currently approved for this purpose, the FDA is considering it.

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How Lamictal May Treat Anxiety

To determine how lamotrigine may alleviate symptoms of anxiety, its necessary to examine its mechanism of action. Although the mechanism of lamotrigines action isnt fully elucidated, research indicates that it functions predominantly as a presynaptic inhibitor of voltage-gated sodium channels whereby it stabilizes neuronal membranes and inhibits the release of glutamate. Most would speculate that modulation of voltage-gated sodium channel activity and the corresponding downstream effects associated with this modulation generate the majority of its anxiolytic effect.

Additionally, some studies suggest that lamotrigine modulates voltage-gated calcium channels, enhances GABA, and inhibits serotonin reuptake each of which may also contribute to the attenuation of anxiety. That said, it is reasonable to assume that the significance of anxiolytic benefit derived from lamotrigine will be contingent upon the underlying neurochemistry and physiology of the user. Persons with anxiety who exhibit abnormalities in the neurochemical systems targeted by lamotrigine should be expected to derive more substantial anxiolytic benefit than others.

Stimulants As Treatment Of Treatment

(PDF) Lamotrigine In Adolescent Treatment?Resistant Depression

The stimulants most commonly used for treatment-resistant depression include:


Lamotrigine is an anticonvulsant medication used to treat epilepsy. It can also be prescribed as a mood stabilizer in those with bipolar disorder as a replacement for Lithium, which has been relatively under-prescribed in recent years.

Studies have shown that the mood-stabilizing component of Lamotrigine is effective in treating treatment-resistant depression. The drug works by accelerating the onset of antidepressant action.


Ritalin is a trade name for methylphenidate. Some doctors prescribe Ritalin for treatment-resistant depression, but it is typically a stimulant used to treat attention deficit hyperactivity disorder and narcolepsy.

Although the adjunctive use of psychostimulants like Ritalin is still being investigated for the treatment of treatment-resistant depression, there is no clear evidence that methylphenidate is effective at easing the symptoms. Although some promising results were seen in case studies, controlled studies have not demonstrated significant improvement in patient outcomes. As such, most doctors do not recommend Ritalin as a first-line treatment for depression. You should never take methylphenidate medications without guidance from your doctor.


The Final Word on Stimulants for Treatment-Resistant Depression

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There Are Established Methods For Managing Treatment

While the words treatment-resistant might seem synonymous with no hope, the reality is that tools do currently exist to help people with TRD. A 2012 study published in the journal Patient Preference and Adherence identified five main treatment strategiesoptimization, switching, combination, augmentation and somatic therapiesthat psychiatrists can use to create a personalized plan for patients.

Optimization, for instance, means that some people with TRD may benefit simply from giving their antidepressant more time to work or by taking a larger dose, Dr. Papp says.

For others, switching to a different class of antidepressantor adding one to the current treatment for a combined approachmay lead to remission. And augmentation may involve using medications that were developed for other uses, but that have since been approved for the treatment of TRD.

Transcranial magnetic stimulation can be an effective nondrug treatment for TRD

There are also somatic therapies, including transcranial magnetic stimulationwhich targets nerve cells in the region of the brain involved in mood control and depressionand electroconvulsive therapy , which induces changes in brain chemistry to help reverse symptoms of TRD.

Have You Tried Lamictal For Anxiety

If you were prescribed lamotrigine to treat a neuropsychiatric condition and were surprised to find that it reduced your anxiety, share your experience in the comments section below. From your perspective, would you say that lamotrigine was: ineffective, slightly helpful, or effective for the treatment of your anxiety? Assuming you had to rate the anxiolytic efficacy of lamotrigine on a scale of 1 to 10 , which numeric rating would you assign it?

To help others get a better understanding of your situation, provide some personal details such as: the dosage and format of lamotrigine you take , whether you administer other substances along with it , your anxiety disorder diagnosis , and the duration over which youve been taking it. If you happened to find lamotrigine as effective for the attenuation of your anxiety, how long did it take after treatment initiation for you to notice an anxiolytic effect? Do you have another neuropsychiatric condition for which your doctor originally recommended lamotrigine, or did your doctor prescribe it off-label specifically for anxiety?

How many medications did your doctor require you to try before deciding to test lamotrigine? Among those that have used lamotrigine for a long-term , were you able to maintain a stable dose with consistent anxiolytic efficacy or did you end up increasing its dosage as a result of tolerance? In your experience, do the anxiolytic effects generated by lamotrigine outweigh its side effects?

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Depression May Have Causes We Dont Yet Understandwhich May Be Why Antidepressants Dont Work For Everyone

I saw many patients with treatment-resistant depression who told me that friends and family members believed they preferred being depressed, or werent trying hard enough to improve, because their antidepressants werent working. This isnt about a lack of motivation.

Jaskaran Singh, M.D., Senior Director of Neuroscience, Janssen PharmaceuticalsShare

While the biology of depression is still largely a mystery, the most popular theory is that its caused by low brain levels of such neurotransmitters as serotonin and norepinephrine, which are associated with feelings of happiness and well-being. But recent research suggests that these neurotransmitters may not be the lone culpritso antidepressants, which work to increase serotonin or norepinephrine levels, may not be a one-size-fits-all treatment.

One of the more modern theories is that depression creates inflammation in the brain, or that inflammation in the brain creates depression, Dr. Papp says. Traditional antidepressants only affect neurotransmitters, so this may be why some patients dont respond to them.

Whether or not this turns out to be true, what we do know is there’s still no guaranteed fix for the problemwhich can be frustrating for both patients and their loved ones.

What Is Esketamine Treatment Like

Hope for Treatment Resistant Depression

Esketamine, like ketamine, has the potential to distort your perception during the first two hours after treatment, so it has to be administered in a clinic setting. Treatment for esketamine nasal spray is done on an outpatient basis.

With the nasal spray, you give yourself three doses, spaced five minutes apart, under doctor supervision. You remain in the clinic under doctor observation until potential side effects have passed.

Esketamine must be used in conjunction with a conventional antidepressant. The intention is that esketamine provides rapid relief from depression symptoms until the other medication takes effect.

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How Stimulants For Treatment

Stimulants are often used for treatment-resistant depression, usually along with another oral antidepressant, such as an SSRI.

Stimulants and psychostimulants for treatment-resistant depression have been used in addition to conventional antidepressants for decades, and with great success. In a study carried out on those with treatment-resistant depression, 38 out of 65 patients showed significant improvement in response to psychostimulants. Despite concerns in the medical field, none of the subjects in this study showed serious side-effects or developed drug dependency.

This doesn’t mean that stimulants are always safe, or that they always work. These kinds of medications can have severe side-effects and dangerous interactions with other drugs, so they must always be taken under guidance from a medical professional.

Does Esketamine Have Side Effects

People can experience a wide range of side effects from esketamine therapy. The most dramatic are hallucinations and feeling disconnected from yourself or reality. However, side effects tend to peak at 40 minutes and wear off within two hours of treatment.

  • Nausea
  • Feeling drunk
  • Headache

If you feel treatment for depression isnt working, talk to your psychiatrist to see if esketamine therapy is an option for you.

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Effect Of Lamotrigine On 5

The antidepressant drug lamotrigine is found to be therapeutically more effective in the treatment of depressive phase of the bipolar disorder than in treating hypomania or mania . The use of lamotrigine as an augmentation drug was suggested from the evidence of the efficacy of the drug in the treatment of major depressive disorders, which also includes refractory unipolar depression . The onset of antidepressant action accelerated when administered in combination with other classical antidepressants . Pilot studies have reported the augmentation therapy of lamotrigine with SSRIs to be well tolerated and far more superior in efficacy than that of SSRI monotherapy .

performed electrophysiological studies in the rat brain to evaluate modulation of the antidepressant-like effects of sustained administration of carisbamate and lamotrigine on monoaminergic mystems. They concluded that 5-HT firing in the DRN is decreased but 5-HT transmission in the forebrain is enhanced by sustained carisbamate and lamotrigine administration.

Is There A Typical Dose Of Lamotrigine

(PDF) Lamotrigine versus lithium augmentation of ...

Your doctor will initially prescribe a low dose of lamotrigine and gradually increase your dose every week or two for several weeks, until you reach an effective dose level.

Treatment guidelines for target blood levels of lamotrigine have not been established for conditions other than epilepsy, Dr. Goldberg points out. In relapse prevention studies conducted by its manufacturer, however, 200 mg/day was found to be a better target dose than 50 mg/day, while higher doses did not provide greater benefit against relapse.

The dosing regimen of lamotrigine can depend on which other medications you are taking to treat bipolar disorder, and is adjusted when you wean off and discontinue other medications. It may also depend on indication and patient age.

Some medicines slow down the metabolism of lamotrigine , requiring a slower rate of increase and a lower target dose, notes Dr. Goldberg. Others speed up its metabolism , requiring a faster-than-usual dose increase and a higher-than-usual target dose.

Also, estrogen derivatives induce lamotrigine metabolism. Dosage adjustments will be necessary in most patients who start or stop taking estrogen-containing oral contraceptives while taking Lamictal.

Lamotrigine comes in several forms for treating bipolar disorder: Tablets, chewable tablets, dissolving tablets. Your doctor may tell you to take tablets once a day, twice a day or every other day.

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How Does Esketamine Treat Depression

Esketamine, and its related drug ketamine, are highly effective depression treatments for a number of reasons:

Esketamines antidepressant function works through a different mechanism than other drugs. Conventional antidepressants increase levels of naturally occurring chemicals such as serotonin, norepinephrine and dopamine. These chemicals are messengers that relay communication between brain cells. The theory is that having greater quantities of these neurotransmitters allows for better communication between brain cells and positively affects mood.

Esketamine works in a similar fashion, but unlike other antidepressants it increases levels of glutamate, the most abundant chemical messenger in the brain. The result? A greater impact on more brain cells at one time.

Lamotrigine Augmentation In Resistant Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
First Posted : May 13, 2009Last Update Posted : May 13, 2009
  • Study Details
Condition or disease
Drug: lamotrigineDrug: placeboDrug: paroxetine Not Applicable
Layout table for study information

Study Type :
Lamotrigine as an Antidepressant Augmentation Agent in Treatment Refractory Unipolar Depression
Study Start Date :
lamotrigine augmentation 25 to 100 mg tablets, 25 to 200 mg bid,10 weeksOther Name: Lamictal Drug: paroxetineopen label paroxetine 10 to 50 mg, at bedtime for 18 weeks Other Name: paxil
placebo: 1-2 tablets bid 10 weeks Drug: paroxetineopen label paroxetine 10 to 50 mg, at bedtime for 18 weeks Other Name: paxil
  • MADRS score
  • Ham-D score
  • CGI-S and CGI-I
  • Information from the National Library of Medicine

    Layout table for eligibility information

    Ages Eligible for Study: 18 Years to 65 Years
    Sexes Eligible for Study:
  • Male or female subjects, age 18-65
  • A current primary diagnosis of unipolar major depression based on certain criteria
  • Exclusion Criteria:

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    Does Lamotrigine Interact With Any Medications Or Other Substances

    Certain other drugs can affect the way lamotrigine works in your body by decreasing its effectiveness or delaying its excretion from your body. These include hormonal birth control methods, estrogen-containing contraceptives, hormone treatments, the antibiotic rifampin, seizure medications such as phenobarbital, and valproic acid, which is also used to treat bipolar disorder.

    Your doctor will carefully prescribe and monitor your dosage when lamotrigine is taken with other treatments. Avoid alcohol, cannabis, and other substances that can increase dizziness or drowsiness while taking lamotrigine. To rule out dangerous side effects, discuss all other medications or mind-altering substances you consume with your doctor before taking lamotrigine.

    One recent British study found that folic acid supplements can cancel out lamotrigines benefits . No one expected that result, as folic acid usually helps depression, and other medications, like valproate , says Dr. Aiken. More research is needed before we can fully trust this result, but until then, we recommend taking lamotrigine without any folic acid supplements, including those found in multivitamins. Once youre doing well on lamotrigine, if you decided to add folic acid, watch out for a potential loss of benefits.

    Lamotrigine Augmentation Therapy In A Case With Treatment

    Treatment Resistant Depression

    It has been shown that lamotrigine may be useful as augmentation of antidepressants for treatment-resistant unipolar depression. A large trial suggested a great response to lamotrigine augmentation in more severely depressed and more refractory unipolar patients.

    We report a case with refractory unipolar depression that had failed to sufficiently respond to several antidepressants, three augmentation strategies and electroconvulsive therapy , but that successfully achieved remission with lamotrigine augmentation of fluvoxamine. The use of lamotrigine was approved by the Ethics Committee of the University of the Ryukyus. Informed written consent and a singed release from the patient authorizing publication have been obtained. His anonymity has been preserved.

    The possibility that he suffered from latent bipolar depression was not ruled out. However, the addition of lamotrigine to fluvoxamine improved his depressive symptoms, and finally led to remission. Therefore, it is suggested that lamotrigine can be a pharmacotherapeutic option for such patients. At a plasma lamotrigine concentration level below the therapeutic range, the therapeutic response was limited. Due to the increased dose of lamotrigine, the patient’s condition remitted at the therapeutic range. This result supports the notion proposed by the authors that therapeutic drug monitoring is necessary to optimize lamotrigine dose in the treatment of refractory depression.

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    With A Nudge From Ai Ketamine Emerges As A Potential Rare Disease Treatment

    The stubbornly high, and steadily increasing, rate of suicides in the U.S. is one factor driving the shift. In April, the National Institute of Mental Health awarded eight grants to test new ways to reduce suicidal thoughts and behaviors in a fast-acting manner, including ketamine and using magnets to activate parts of the brain.

    Overall, an unofficial estimate shows the agencys funding for research involving roughly doubled from $34.3 million in the 2007 fiscal year to $68.5 million in FY 2020, based on a search of the National Institutes of Health RePORTER database. A search for transcranial magnetic stimulation for depression reveals an estimated ninefold increase to $21.4 million over the same period.

    Nolan Williams, a psychiatrist and neurologist at Stanford University, received one of the new grants as well as another from the NIMH to study magnetic stimulation in treatment-resistant depression. He said there is a push in the field to to think beyond the typical view of depression, and consider new treatments. Were enhancing view to have a multilevel understanding of the problem, he said. Its about incorporating it into a deeper, more dynamic understanding .

    The entire thinking of the approach to treating depression is pretty much confined in that little box, said Lisa Harding, a psychiatrist at the Yale School of Medicine.

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