The 5 Best Medications for Depersonalization (DPDR)

Hello there, I’m Ben, I beat DPDR and so can you!

What is the best medication for depersonalization? A pharmacist shares his opinion in regards to:

Naltrexone and Naloxone
Lamotrigine (Lamictal)
Selective Serotonin Reuptake Inhibitors (SSRIs)
Benzodiazepines and
Clomipramine (Anafranil)

I am not a doctor and I did not use any of the medications mentioned in this post. Please, don’t use any of the mentioned medications, without consulting your physician.

I contacted a pharmacist to write an article reviewing and explaining the effects of 1. Naltrexone and Naloxone 2. Lamotrigine 3. Selective Serotonin Reuptake Inhibitors (SSRIs) 4. Benzodiazepines and 5. Anafranil on mental illnesses.

Here is what he wrote:

Medications for Depersonalization-Derealization Disorder

There is no proper treatment plan for depersonalization/derealization disorder, but medications can reduce distressing symptoms like anxiety, depression or post-traumatice stress disorder and even lead to full remission of the disorder.

Patients are apparently helped by selective serotonin reuptake inhibitors (SSRIs), lamotrigine, opioid antagonists like naltrexone and naloxone, anxiolytics, and stimulants.

However, these drugs may work largely by targeting other mental disorders (e.g, anxiety, depression) that are often associated with or precipitated by depersonalization and derealization.

1. Naltrexone and Naloxone

Naltrexone and naloxone are opioid antagonists primarily used in treatment of opioid overdose such as morphine etc. But do you know that they may help with the treatment of depersonalization/derealization as well?

Naloxone and Naltrexone are opioid antagonists that have shown some efficacy in treating DPDR.

There is some evidence for dysregulation of endogenous opioid system in the brain suffering from depersonalization, and a few studies suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms.

Studies suggested that blocking opioid receptors in the brain leads to a decline in opiate-modulated dissociative states. That means taking Naltrexone or Naloxone can lead to experiencing less of dissociative states such as depersonalization, derealization, and their various symptoms.

Stress can be accompanied by secretion of endogeneous opioids, mostly beta-endorphins. These observations led us to suggest that disturbance in the opioid system such as the increased endorphin secretion and/or a change in the sensitivity of opioid receptors play an important role in the pathogenesis of depersonalization.

There are few neurochemical and neurohormonal studies of chronic depersonalization, and they have suggested possible dysregulation of several systems including the hypothalamic-pituitary-adrenal axis, noradrenergic, serotonergic, glutamatergic, and endogenous opioids. The endogenous opioid system is well known to mediate stress-induced analgesia. 0pioid antagonists have been reported to reduce symptoms of dissociation and depersonalization in a few preliminary studies.

In one study of subjects with borderline personality disorder, decrease in dissociation was reported using high dose naltrexone.

Specifically in DPDR, one study reported a marked decline in chronic depersonalization in subjects treated intravenously with naloxone, although the duration of the response was not clearly explicated. Of note, naloxone, naltrexone, and nalmefene are all nonspecific opioid antagonists, whereas selective k opioid antagonists have not yet been developed for human use.

Open Treatment trial

In the open treatment trial, described by Daphne Simeon in the “Journal of Clinical Psychopharmacology”, 14 subjects were recruited and treated with Naltrexone for 6 weeks to a maximum dose of 100 mg/d (first 7 subjects) or 10 weeks to a maximum dose of 250 mg/d (next 7 subjects). The rationale for the use of high dose naltrexone , as well as the increase in naltrexone dosing halfway through the trial , is that naltrexone is a non-specific opioid antagonist which blocks “mu” receptors at low doses but requires high doses to block other opioid receptors such as the “kappa” receptors. Mean naltrexone dose was 120 mg/d.

There was an average 30% reduction of symptoms with treatment, as measured by 3 validated dissociation scales.

Three out of fourteen patients who were administered naltrexone were found to be free of depersonalization symptoms, whereas seven showed marked improvement.

Adverse effects reported by the 14 trial participants were, sedation/fatigue (N=70), nausea (N=5), depression (N=3), diarrhea (N=1), tingling (N=1), and nightmares (N=1). Two subjects reported no side effects

Conclusion

There is some evidence for dysregulation of endogenous opioid systems in depersonalization, and a few studies have suggested that opioid antagonists may have efficacy in the treatment of dissociation and depersonalization symptoms.

2. Lamotrigine

Lamotrigine, an anticonvulsant and mood stabilizer used to treat epilepsy and bipolar disorder, along with experimental uses for schizophrenia, depression, and borderline personality disorder.

Lamotrigine comes under the brand name Lamictal.

Lamotrigine belongs to a class of drugs called anticonvulsants or antiepileptic drugs (AEDs). It is used to treat seizures and bipolar disorders.

For people with epilepsy, this drug reduces the release of a substance in your brain known as glutamate. This action prevents the neurons in your brain from becoming too active. As a result, you may have fewer seizures.

For people with bipolar disorder, this drug may affect certain receptors in your brain that help control your mood.

With this condition, a person has extreme emotional highs and lows. This could decrease the number of mood episodes you have.

Lamotrigine acts at the presynaptic membrane to reduce the release of glutamate (excitory neurotransmitter), and it has been shown to reverse depersonalization-related phenomena induced by the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine in healthy individuals (Anand et al, 2000).

A different body of research suggests that glutamate might be relevant to dissociation. Sub-anesthetic doses of the N-methyl D-aspartate receptor antagonist ketamine were shown to induce subjective experiences characteristic of depersonalization.

It is believed that the altered state of consciousness induced by ketamine is mediated by increased glutamate release in response to NMDA receptor blockades, with a consequent excess of glutamate activity at non-NMDA glutamate receptors.

Lamotrigine has been reported in the treatment of DPDR because of its ability to impede glutamate release at the presynaptic membrane and to reduce the effects of ketamine on consciousness (Anand et al. 2000; Wang et al. 1996).

Neither lamotrigine alone nor serotonergic antidepressants alone have been shown to be reliably effective in treating depersonalization disorder, but study suggests that when used in combination, these medications can produce a profound reduction in symptoms.

Dosage:

Initial: 50 mg PO qDay for 2 weeks, THEN
100 mg/day divided q12hr for 2 weeks

Side effects of Lamotrgine

Lamotrigine oral tablet may cause drowsiness. Do not drive, use heavy machinery, or do other dangerous activities until you know how this drug affects you.
The more common side effects that can occur with use of lamotrigine include:

• dizziness
• drowsiness
• headache
• double vision
• blurred vision
• nausea and vomiting
• diarrhea

Case Study

Case series of 32 patients with depersonalization disorder who had been treated with lamotrigine, most of them were previously taking an antidepressant medication (SSRIs, SNRIs, or tricyclic antidepressants). 56% of patients overall showed a response of a 30% or greater reduction in their symptoms on CDS score during treatment with lamotrigine, which lasted for an average of 13.7 months.

Of those patients taking lamotrigine in combination with an SSRI, 81.8% achieved a reduction of 30% or more in their symptoms on CDS score.

Lamotrigine should be initiated at a starting dose of 25 mg/day, with the dose gradually increased at fortnightly intervals, and a greater lamotrigine dose was significantly correlated with a greater decrease in CDS score.

Conclusion

Lamotrigine as sole agent was not found to be effective in a previous randomized trial. However, evidence from open trials suggests it may be beneficial as an “add-on” medication with anti-depressants like SSRIs. Lamotrigine is prescribed as an augmenting medication.
Lamotrigine in combination with SSRIs is also one of the very few approaches that has shown some efficacy in treating chronic depersonalization, the syndrome of unremitting depersonalization and derealization symptoms that can last for decades. Depersonalization disorder is highly distressing to sufferers and associated with a wide array of negative mental health and social outcome

3. Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective Serotonin Reuptake Inhibitor (SSRI) – DPDR

Most people with dissociative disorders have co-occurring conditions, and depression is one of the most common. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), are frequently prescribed to treat comorbid depression.

Popular SSRIs for dissociative disorders include:

• Sertraline (Zoloft)
• Fluoxetine (Prozac)
• Citalopram (Celexa)

SSRIs work by enhancing the function of nerve cells in the brain by inhibiting serotonin reuptake which has a role in mood elevation. Information is communicated between your nerve cells in the brain. The chemical messengers that deliver these signals are called neurotransmitters. Serotonin is one type of neurotransmitter.

When these brain cells (called neurons) send signals to one another, they release a little bit of a neurotransmitter so that the message can be delivered. They then have to take back the neurotransmitter they released so they can send the next message. This process of replacing the neurotransmitter is called “reuptake.”

If you’re struggling with depression, the areas of your brain that regulate mood and send messages using serotonin might not function properly.

SSRIs help make more serotonin available by blocking the reuptake process. This allows serotonin to build up between neurons so messages can be sent correctly.

The sense of detachment that accompanies depersonalization is often closely linked with flat affect and blunted emotion, all of which can be improved with SSRIs. Antidepressants can also stabilize mood and reduce the intrusive symptoms that trigger dissociative symptoms.

Side effects of SSRIs:

SSRIs are generally safe for most people. Possible side effects of SSRIs may include, among others:

• Nausea, vomiting or diarrhea
• Headache
• Drowsiness
• Dry mouth
• Insomnia
• Nervousness, agitation or restlessness
• Dizziness

Conclusion

Open-label trials suggest that the use of SSRIs in combination with lamotrigine is particularly beneficial in a substantial number of patients. Similarly, the use of clonazepam, particularly in conjunction with SSRI antidepressants, appears to be beneficial in patients with high levels of background anxiety. SSRIs can also be used to treat anxiety, which is another commonly co-occurring condition with depersonalization-derealization disorder. They are often the best medical option for treating dissociative disorders with comorbid anxiety.

As well as depression, SSRIs can be used to treat a number of other health conditions, including:

• Generalized anxiety disorder (GAD)
• Obsessive compulsive disorder (OCD)
• Panic disorder.
• Severe phobias, such as agoraphobia and social phobia.
• Bulimia- potentially life threatening eating disorder.
• Post-traumatic stress disorder (PTSD)

4. Benzodiazepines

Sometimes called “benzos,” are a class of psychoactive drugs. Benzodiazepines work with the GABA receptors in the brain, GABA is an inhibitory neurotransmitter. Benzodiazepines enhance the effect of the neurotransmitter gamma amino butyric acid (GABA) at the GABAA receptor, resulting in sedative, hypnotic, anti-anxiety as well as muscle relaxant properties.

Common drugs belonging to this class are Xanax, Klonopin, Valium. These compounds are often prescribed for anxiety, panic disorders, and obsessive-compulsive disorders.

It has been found that having high levels of anxiety sometimes results in depersonalization. This might explain why people taking benzos for DPDR do sometimes experience some relief from it. Whether or not these compounds alleviate the underlying dissociation is still in question.

Side effects of benzodiazepines

Side effects of benzodiazepines are serious withdrawal effects and being highly addictive. If you take them every day for months, then you have to add up the dose to get the same effect as before. If you try to withdraw, then your DP and anxiety might increase. Benzos are ideally taken on an “as needed” basis, and are more effective in people with DP who are highly anxious.

5. Clomipramine

Clomipramine comes under the brand name Anafranil, is a tricyclic antidepressant.

It works by restoring the balance of certain natural substances (serotonin, nor-epinepherine among others) in the brain. It helps decrease persistent/unwanted thoughts (obsessions), and it helps reduce the urge to perform repeated tasks (compulsions such as hand-washing, counting, checking) that interfere with daily living. Clomipramine has also been used to treat depression, panic attacks, and ongoing pain.

DOSE:

Initially, 25mg/day PO and gradually increase upto 100mg/day or 3mg/kg/day. Usually taken a single dose at bedtime, but may be given in divided doses.
Obsessive thinking and having intrusive thoughts or imagery is a common symptom of DPRD. Anafranil is a drug that has been shown in some studies to help alleviate these kinds of thoughts. But tricyclic anti-depressants have more side effects than SSRIs. More studies required to be well aware of its effectiveness in depersonalizarion/derealization disorder.

General Conclusion

At this time, there isn’t any psychopharmacological medication that can treat DPRD specifically and effectively.

But these medications can reduce distressing symptoms and even lead to full remission of the disorder.

These medications are the best medical choice for dissociative disorders with comorbid anxiety or depression.

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Medications for Depersonalization-Derealization Disorder

1. Naltrexone and Naloxone

Open Treatment trial

Conclusion

2. Lamotrigine

Dosage:

Side effects of Lamotrgine

Case Study

Conclusion

3. Selective Serotonin Reuptake Inhibitors (SSRIs)

Side effects of SSRIs:

Conclusion

4. Benzodiazepines

Side effects of benzodiazepines

5. Clomipramine

DOSE:

General Conclusion

You Want to Ask me a Question?

Related Questions

References