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From the Townsend Letter
February / March 2013

What to Do When Patients Wish to Discontinue Their Psychotropic Medications? Effective Tapering Strategies to Limit Drug Withdrawal and Destabilization: a Clinician's Perspective
by Jonathan E. Prousky, ND, MSc
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Improving the Odds of a Successful Outcome
It is common for patients to experience problems even after small reductions in their psychotropic drugs. This is usually misattributed to a reemergence of their underlying psychiatric disorder as opposed to problems related to psychotropic drug withdrawal.1 When this happens, it is common for such patients to be shamed by family members, psychiatrists, and support workers into the notion that they cannot maintain their psychological health without depending on psychotropic drugs for the rest of their lives, thus forcing patients to continue long-term treatment.1 Darton reported that patients with mental health issues are too often denied the chance to come off their medications, take risks, and potentially make their own mistakes.9 If family members are supportive and encouraging, this will reduce risks associated with tapering psychotropic drugs.9

Diet and lifestyle modifications can also significantly improve a patient's chances of successfully tapering off psychotropic drugs. Factors that have been identified as helpful include: (1) eating regularly; (2) avoiding sugary foods and drinks; (3) abstaining from all recreational drugs, alcohol, and possibly even caffeine; (4) establishing good sleep habits; and (5) drinking plenty of fresh water throughout the day.9,10

Supporting the Tapering Process with Specific Natural Health Products
I have found specific natural health products helpful when used during and after the tapering process to mitigate withdrawal, prevent potential relapses, and improve a patient's chances of not requiring his/her psychotropic medication any longer.

 Melatonin works well for insomnia, which is common during the tapering process. The hormone is being formally studied among schizophrenic patients withdrawing from long-term benzodiazepine use.11 Previous reports have shown some efficacy in reducing benzodiazepine-withdrawal-associated sleep disruption.12,13 Ideally, controlled- or prolonged-release preparations should be used, with doses varying from 1 to 5 mg at bedtime. If taken 1 or 2 hours before bedtime, these forms of melatonin enable a more sustained blood level of the hormone and promote sleep that tends to be deeper and less fragmented. I tend not to prescribe quick-release melatonin preparations, since they rapidly increase blood levels but do not promote a more restful and longer sleep. On occasion, I will combine a small dose (1 mg) of quick-release melatonin with a controlled- or prolonged-release preparation (3–6 mg), to facilitate quick sleep onset with sustained hormone levels to offset a broad array of sleep issues (e.g., racing mind, restlessness, and waking too early) that patients tend to experience during the tapering process.

Niacinamide (nicotinamide) can also be given to reduce withdrawal symptoms from all psychotropic drugs, since it generally "calms" the nervous system and does not possess any concerning drug interactions. It is sometimes very useful among patients withdrawing from benzodiazepines, since it possesses benzodiazepine-like effects.14 One case report demonstrated its clinical effectiveness in allowing a patient to remain clinically stable while tapering off clonazepam.14 The patient weaned himself off clonazepam in 2 weeks while increasing his daily amounts of niacinamide until he was taking 2500 mg each day. When this report was published, the patient had been free of clonazepam for 6 months and had remained stable on only the niacinamide. A written correspondence from the late Dr. William Kaufman (January 10, 1998) noted the following about the vitamin's mechanism of action:

Niacinamide has ungated access to the brain. When it enters the brain, it has a strong affinity for the benzodiazepine receptors and causes a desirable calmative effect which you have observed. But it also improves other functions of the central nervous system.

Effective daily doses of niacinamide range from 1500 to 2500 mg. It is rarely necessary to go beyond 2500 mg, since higher doses can be associated with nausea and potentially vomiting. The mean elimination half-life in human subjects given 3000 mg of the vitamin was 5.9 ± 0.6 hours.15 Since it has such a short elimination half-life, niacinamide must be administered several times throughout the day; otherwise, its therapeutic effects will be lessened.

To stabilize mood resulting from withdrawal and to ease mood swings during tapering, I use a product called Neurapas Balance. Its therapeutic effects limit anxiety, depression, muscle tension, stress reactions, and other withdrawal reactions resulting from the tapering process. Each film-coated tablet contains 60 mg of the dry extract of Hypericum perforatum, 28 mg of the dry extract of Valerian officinalis, and 32 mg of Passiflora incarnata. There have been approximately 10 company-sponsored clinical studies (i.e., 2 controlled and 8 observational cohort studies) and 2 experience reports, which have shown this herbal combination to be safe and effective for both depression and anxiety.16 Each individual herbal extract possesses well-known postulated mechanisms of action.17 The extract of Hypericum perforatum exhibits monoamine oxidase inhibition, gamma-aminobutyric acid (GABA) activity, monoamine reuptake, upregulation of 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A receptors, and modulation of cytokine production. Valerian is known to have GABAergic effects. Passiflora is a partial agonist to benzodiazepine receptors. Generally, my patients start with 1 pill twice daily, and over the course of many weeks, the dose is increased to 3 pills twice daily. Even though the elimination half-life is not known for this preparation, multiple daily dosing appears to yield more optimal therapeutic outcomes.

Clinicians should not be overly concerned about adverse drug inter­actions, since this specific preparation contains a very low daily dose of Hypericum (i.e., 360 mg from 6 tablets) with a correspondingly low hyperforin content.18 Studies demonstrating signifi­cant pharmacokinetic drug inter­actions with Hypericum extracts typically involve daily dosages of 900 mg or more. At the recommended daily dose of 6 tablets, the mean amounts of hypericin and hyperforin delivered are 0.72 mg and 1.35 mg respectively. This small amount of hyperforin does not induce the major liver drug-metabolizing enzyme cytochrome P(CYP)450 3A4. Hypericum preparations containing much higher amounts of hyperforin do induce this enzyme, and those are believed to be the reason for numerous potential drug interactions. Unfortunately, the low-dose preparation is not available in the US.

Rhodiola rosea extract can also stabilize patients during psychotropic tapering. Clinical trials have shown it to attenuate mild and moderate depression, generalized anxiety, and burnout/fatigue – common withdrawal symptoms that many patients experience during tapering.19–21 It specifically works by inhibiting enzymes involved in the degradation of monoamine neurotransmitters (i.e., serotonin, dopamine, and norepinephrine), and this prevents the depletion of adrenal catecholamines following acute stress.22 The therapeutic dose range is somewhere between 500 and 680 mg of a standardized extract containing 3% percent total rosavins and 1% salidrosides. I normally recommend that Rhodiola rosea extract to be taken with breakfast, as it can cause considerable nausea and possibly vomiting on an empty stomach. I usually prescribe 500 mg at breakfast to stabilize mood and lessen anxiety, and will increase the daily dose to 650 to 680 mg if the patient's response is not marked enough. Although a rat study determined the elimination half-life of salidroside in Rhodiola rosea extract to be 39.69 ± 21.02 minutes, I have not found multiple dosing throughout the day necessary.23 I doubt that the elimination half-life from the rat study correlates to the elimination half-life in humans.

There is one published report of an interaction between Rhodiola rosea extract and escitalopram.24 The case involved a 26-year-old Chinese female who presented to the emergency department with a 1-hour history of heart palpitations and light-headedness. The patient was diagnosed with supraventricular tachycardia (SVT) as per electrocardiogram findings. Her pulse rate was 150 beats per minute, and her troponin I was significantly elevated (0.39 mg/L; normal < 0.06). All other investigations were normal. She was treated with 6 mg of intravenous adenosine, which normalized her sinus rhythm. No more SVTs happened at follow-up, and her troponin I normalized in 2 days. While this case points to possible interactions between Rhodiola rosea extract and SSRI medication, I have not observed any untoward interaction when patients take them concomitantly during the tapering process. Therefore, it is important to inform all patients of this possibility and instruct them to contact you immediately should they experience a sudden onset of heart palpitations and increased heart rate.

GABA is very useful to moderate mood instability while also decreasing anxiety if given during the tapering process. Since GABA can also promote sleep, it may be given several hours before bedtime to decrease sleep fragmentation and sleep-onset problems. For patients tapering from lithium, GABA works particularly well for mood regulation. It functions as an inhibitory neurotransmitter in the central nervous system. The mechanism of GABA's neuroinhibition is mediated through an increase in the permeability of postsynaptic membranes to chloride ions, leading to hyperpolarization. There continues to be uncertainty whether GABA can traverse the blood–brain barrier when administered orally; it appears to act on the central nervous system without crossing the blood–brain barrier.25 There are 2 forms of GABA available: crystalline GABA and PharmaGABA (produced by a fermentation process that utilizes Lactobacillus hilgardii).26 Both forms have the same molecular structure and mechanism of action, and therefore it is illogical to contend that one form somehow traverses the blood–brain barrier while another does not.25 GABA might have a therapeutic effect comparable to benzodiazepine medications and might be useful for patients addicted to them as well.27 In a case report, a 40-year-old female patient with a history of severe anxiety was able stop her diazepam and replace her lorazepam with 200 mg of GABA four times each day.27 The optimal dose of GABA is normally 2 to 3 grams daily away from meals.27 I do not use PharmaGABA due to its impracticality, for it only comes in 100 mg or 200 mg pills.

Even though side effects from GABA are rare, there is one report of neurologic tingling, flushing, and transient hypertension and tachycardia in a subject taking very high oral doses (10 grams on an empty stomach).27 Smaller oral doses (1–3 grams daily) have been reported to cause neurologic tingling and flushing in several volunteer subjects.27 PharmaGABA has been tested in rats that were administered doses of 5000 mg/kg.26 There were no deaths and the lethal dose that would likely kill at least 50% of the rat population was determined to be greater than 5000 mg/kg of body weight.

I sometimes use the amino acid L-theanine, since it can decrease anxiety and also improve focus and concentration. It is not uncommon for patients to experience disturbances in cognition during the tapering process, making this intervention potentially valuable. L-theanine presumably increases both dopamine and serotonin, although a study in rats showed that it might decrease serotonin. It also increases alpha brain-wave activity, which is associated with relaxation.28 In a study involving schizophrenic and schizoaffective disorder patients, the use of L-theanine as an augmentation strategy was associated with reductions in the following: anxiety (p = 0.015), positive symptoms (p = 0.009), and general psychopathology scores (p < 0.001).29 In another study using the same 40 patients with schizophrenia and schizoaffective disorder, the beneficial effects of L-theanine were coupled with circulating levels of brain-derived neurotrophic factor and the cortisol-to-dehydroepiandrosterone ratio.30 My clinical experience has shown L-theanine to mitigate destabilization while tapering from FGA and SGA drugs. The optimal dose appears to be 200 mg twice daily. There should be no side effects attributed to L-theanine, although caution might be warranted, since one of my patients is certain that it caused her to feel temporarily manic.

Numerous other natural health products could potentially be used alongside psychotropic drugs during the tapering process. Clinicians trained in clinical nutrition and botanical medicine must use discretion during psychotropic drug tapering, monitor patients' progress carefully, mitigate potential interactions, and use available pharmacokinetic information to guide appropriate dosing.

Sample Tapering Schedules
Here are several tapering schedules that I have used in clinical practice. Each schedule was individualized to suit each patient's needs and support mental stability. Periodic visits and regular communications (e.g., telephone calls and e-mails) are required during the tapering process so that each patient's mental stability can be regularly assessed and warning signs of destabilization can be clinically managed to avoid more serious setbacks and/or life-threatening consequences.

Example 1
This patient was taking 25 mg of controlled-release Paxil (paroxetine) for depression. After I corresponded with her family doctor, she was switched to a 20 mg dose of Prozac (fluoxetine). The patient tolerated this switch very well. After 4 weeks on the Prozac, she was switched to a liquid form of the drug. Liquid forms allow for a more successful and gradual tapering process. Even though the tapering schedule as outlined below is much quicker than my usual process, this is what the patient requested. She did well and did not destabilize. She was eventually taken off the Neurapas Balance due to pregnancy. She is currently expecting her first child.

  • Week 1: 16 mg daily of liquid Prozac and 1 pill twice daily of Neurapas Balance.
  • Week 2: 12 mg daily of liquid Prozac and 1 pill three times daily of Neurapas Balance.
  • Week 3: 8 mg daily of liquid Prozac and 2 pills a.m. and 2 pills p.m. of Neurapas Balance.
  • Week 4: 4 mg daily of liquid Prozac and 3 pills a.m. and 3 pills p.m. of Neurapas Balance.
  • Week 5+: Discontinue the liquid Prozac and remain on 3 pills a.m. and 3 pills p.m. of the Neurapas Balance.

Example 2
This patient was taking 50 mg daily of Seroquel XR (quetiapine fumarate – extended-release for depression and severe anxiety. With the cooperation of her psychiatrist, she was first switched to the non-extended-release form of Seroquel, since the 25 mg tablets can be cut into quarters (6.25 mg per quarter), making it easier to taper. The tapering process was done very gradually to mitigate instability. She is currently doing very well, and has discontinued the Seroquel without any instability or a return of her previous depression and severe anxiety.

  • Week 1–3: 43.75 mg of Seroquel, 200 mg of L-theanine, and 500 mg twice daily of niacinamide.
  • Weeks 4–6: 37.5 mg of Seroquel, 200 mg of L-theanine, and 500 mg three times daily of niacinamide.
  • Weeks 7–9: 31.25 mg of Seroquel, 200 mg of L-theanine a.m. and 100 mg of L-theanine p.m., and 500 mg three times daily of niacinamide.
  • Weeks 10–12: 25 mg of Seroquel, 200 mg of L-theanine twice daily, and 1000 mg of niacinamide twice daily. Instructed to add 1.5 mg of prolonged-release melatonin (PRM) 60 minutes before bed.
  • Weeks 13–15: 18.75 mg of Seroquel, 200 mg of L-theanine twice daily, 1500 mg of niacinamide at breakfast, and 1000 mg at dinner. Continued with 1.5 mg of PRM 60 minutes before bed.
  • Weeks 16–18: 12.5 mg of Seroquel, 200 mg of L-theanine twice daily, 1500 mg of niacinamide breakfast, and 1000 mg dinner. Increase to 3.0 mg of PRM 60 minutes before bed.
  • Weeks 19–21: 6.25 mg of Seroquel, 200 mg of L-theanine twice daily, 1500 mg of niacinamide breakfast, and 1000 mg dinner. Continue with 3.0 mg of PRM 60 minutes before bed.
  • Week 22+: Discontinue the Seroquel, continue with 200 mg of L-theanine twice daily, and 1500 mg of niacinamide breakfast, and 1000 mg dinner. Continue with 3.0 mg of PRM 60 minutes before bed.

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Consult your doctor before using any of the treatments found within this site.

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