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Dr. Bob is Robert Hsiung, MD,
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Posted by Novelagent on March 31, 2012, at 7:09:46
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2117825/J Neurol Neurosurg Psychiatry. 2007 May; 78(5): 548.
doi: 10.1136/jnnp.2006.101014
PMCID: PMC2117825Copyright © 2007 BMJ Publishing Group Ltd
Improvement in neuroleptic‐induced akathisia with intravenous iron treatment in a patient with iron deficiency
Paul E Cotter and Shaun T O'Keeffe
Paul E Cotter, Shaun T O'Keeffe, Department of Geriatric Medicine, Galway University Hospitals, Galway, Ireland
Correspondence to: Dr S T O'Keeffe
Unit 4, Merlin Park Regional Hospital, Galway, Ireland; s.okeeffe@mailn.hse.ie
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Iron deficiency may play a role in the pathogenesis of drug‐induced akathisia, but the evidence is conflicting.1,2,3 There have been no reports of the effect of iron treatment in this condition. We report the case of a patient with iron deficiency whose akathisia had not responded to standard interventions but did respond dramatically to intravenous iron treatment.
A 68‐year‐old man with schizophrenia had been well controlled for 10 years on thioridazine 150 mg/day. His treatment was changed to respiridone 1 mg twice daily. Within 2 weeks, he had developed a severe sensation of inner restlessness and anxiety associated with increased leg movements and body rocking. No depressive or psychotic symptoms were noticed, although the patient was greatly distressed. Acute drug‐induced akathisia was diagnosed.No improvement in akathisia symptoms was noticed when the dose of respiridone was reduced or when respiridone was discontinued and thioridazine restarted. Therapeutic trials of alprazolam, benztropine and propranolol failed to alleviate his symptoms and led to side effects.
When seen in our clinic, the patient had had symptoms for >6 months. He reported a terrible feeling of restlessness and anxiety gnawing inside me each day. Symptoms were present throughout the day, with no worsening at night, and no limb paraesthesias were noticed. There was no personal or family history suggestive of restless legs syndrome (RLS). Neurological examination was normal apart from reduced facial expressiveness. The Barnes Akathisia Rating Scale (BARS), a well‐validated scale of akathisia severity comprising objective and subjective components, was 11/14, which is consistent with severe akathisia.2
Electrolytes, serum urea, creatinine and glucose, thyroid function tests, erythrocyte sedimentation rate, C reactive protein, vitamin B12, and folate levels were normal. Haemoglobin was 13.1 g% (abnormal in our laboratory <13 g%), transferrin saturation 12% (abnormal <15%), serum ferritin 36 μg/l (abnormal <12 μg/l), total iron‐binding capacity 490 μg/l (abnormal >400 μg/l) and serum iron 520 μg/l (abnormal <600 μg/l). A diagnosis of iron deficiency was made on the basis of the abnormal transferrin saturation combined with a serum ferritin <50 μg/l.4 Gastrointestinal examination was normal and serial tests for faecal occult blood were negative. He had a distant history of peptic ulcer disease. Dietary history showed inadequate intake of iron‐containing foods. His dentition was poor. The patient refused endoscopic investigation of the intestinal tract. Screening tests for coeliac disease were negative.
Oral iron supplements caused unacceptable nausea and epigastric discomfort. The patient was given 400 mg intravenous ferrous sucrose in divided doses (100 mg in 100 ml normal saline on days 1 and 3, and 200 mg on day 5). On day 7, the patient reported that he felt normal for the first time in months. The BARS score was now 3/14 (corresponding to mild or questionable akathisia); haemoglobin was 13.8 g%, ferritin 52 μg/l and transferrin saturation 17%. Dietary advice was given to increase the intake of iron‐containing food. Subsequently, he was able to tolerate 300 mg ferrous gluconate (containing 35 mg of elemental iron) every second day. Clinical (BARS score 3/14) and haematological (haemoglobin 13.7 g% and ferritin 68 μg/l) improvement were maintained on review at 5 months.
Both akathisia and RLS are characterised by motor restlessness and sleep disturbances, and RLS can be precipitated by dopamine‐blocking drugs. There is convincing evidence that iron status is an important factor in the pathogenesis of RLS, and correction of iron deficiency improves symptoms in RLS.5 The balance of evidence from previous studies does not suggest that iron deficiency plays a similarly critical role in the development of drug‐induced akathisia in most patients. However, many studies either focused on serum iron,1,2 which is not a good guide to iron status, or used an inappropriately low cut‐off for normal serum ferritin.4 Nevertheless, studies that examined ferritin levels reported that patients with akathisia had lower levels than controls without akathisia.3
Studies comparing blood tests with bone marrow examination have shown that serum ferritin at a cut‐off of 50 μg/l is the best screening test for iron deficiency in patients with and without anaemia.4 Furthermore, serum ferritin <50 μg/l has also proved useful for predicting responsiveness to iron supplementation in people with RLS.5
The patient in this report had several haematological indices suggestive of iron deficiency and several risk factors for iron deficiency. His serum ferritin of 36 μg/l is also consistent with mild iron deficiency. His haemoglobin level of 13.1 g% was at the low end of normality for a man. As a general rule, 8 mg of storage iron corresponds to 1 μg/l ferritin. Thus, in an iron replete person, 400 mg of intravenous iron would lead to a rise in serum ferritin of about 50 μg/l; the relatively small rise in ferritin levels in our patient suggests that the iron supplement was indeed used to correct a tissue deficiency in iron.
It is unlikely that this patient had an atypical RLS. No night‐time worsening of symptoms (a necessary diagnostic feature in RLS) was noticed. The feeling of inner restlessness and body rocking are characteristic of acute drug‐induced akathisia. It is not uncommon for akathisia, once provoked, to fail to resolve when the precipitating drug change is reversed.
The close temporal relationship between administration of intravenous iron and resolution of hitherto resistant symptoms in our patient suggests that iron deficiency can contribute to the development or persistence of akathisia in some patients. Iron repletion may be valuable in such cases, although this requires further evaluation. There are, of course, other potential benefits to treating and identifying the cause of iron deficiency. We suggest that haemoglobin, serum ferritin and transferrin saturation should be checked in patients with akathisia, and that patients with iron deficiency should be treated until haemoglobin is normal and serum ferritin is more than 50 μg/l. Although the use of intravenous iron formulations may facilitate examination of the potential effects of iron repletion on akathisia in future studies, biochemical improvement is usually seen within 24 weeks of starting oral iron supplements in patients with deficiency and this should remain the initial treatment.Footnotes
Competing interests: None.
References
1. Brown K W, Glen S E, White T. Low serum iron status and akathisia. Lancet 1987. 112341236.1236. [PubMed]
2. Barnes T R, Halstead S M, Little P W. Relationship between iron status and chronic akathisia in an in‐patient population with chronic schizophrenia. Br J Psychiatry 1992. 161791796.796. [PubMed]
3. Kuloglu M, Atmaca M, Ustundag B. et al Serum iron levels in schizophrenic patients with or without akathisia. Eur Neuropsychopharmacol 2003. 136771.71. [PubMed]
4. Guyatt G H, Oxman A D, Ali M. et al Laboratory diagnosis of iron‐deficiency anemia: an overview. J Gen Intern Med 1992. 7145153.153. [PubMed]
5. O'Keeffe S, Gavin K, Lavan J. Iron status and restless legs syndrome in the elderly. Age Ageing 1994. 23200203.203. [PubMed]
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PubMed articles by these authors
Posted by Novelagent on March 31, 2012, at 8:41:13
In reply to Improvement of akathisia using Fe -journal article, posted by Novelagent on March 31, 2012, at 7:09:46
Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence.
AuthorsGold R, et al. Show all Journal
J Clin Psychiatry. 1995 Oct;56(10):476-83.Affiliation
Department of Psychiatry, University of Vermont College of Medicine, Burlington, USA.Abstract
BACKGROUND: An association found between akathisia and iron deficiency led to the suggestion that iron supplementation might be a useful therapeutic intervention for patients with akathisia. There is, however, a body of literature on the abnormal deposition of iron in the brain in several degenerative diseases like Hallervorden-Spatz syndrome, Parkinson's disease, and Alzheimer's disease. Given the ability of neuroleptics to chelate iron and promote its deposition in the brain, we questioned whether peripheral measures of iron are an accurate reflection of central iron levels and thus whether there was a rationale for iron supplementation in akathisia.METHOD: A MEDLINE search for literature relating to iron and akathisia, tardive dyskinesia, and Parkinson's disease was carried out and critically reviewed.
RESULTS: Evidence is presented for the ability of neuroleptics to chelate iron, mobilize it from peripheral stores, and deposit it in the basal ganglia. The effect of iron on dopaminergic receptor activity in brain and the potential role of iron in degenerative and neuroleptic-induced movement disorders are reviewed. The preponderance of the evidence shows a relationship between iron excess in the basal ganglia and the movement disorders. We found no studies that have examined the regulation of central levels of iron in patients with akathisia.
CONCLUSION: The rationale for iron supplementation in the treatment of akathisia is relatively weak, and there are potentially adverse long-term consequences as outlined in our review. More research is required to directly measure the level of iron in the brain of patients with akathisia, e.g., using magnetic resonance imaging, before such therapeutic intervention can be recommended.
Posted by LostBoyinNCReturns on March 31, 2012, at 11:05:27
In reply to Study: Iron supplement + antipsychotics don't mix, posted by Novelagent on March 31, 2012, at 8:41:13
This makes a lot of sense. Iron deficiency is also associated (generally with) lower dopamine levels. If you then add a dopamine depleting or blocking drug, you probably have a higher chance of developing akathisia.
I believe this study. It is really just common sense.
Eric
> Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence.
>
> AuthorsGold R, et al. Show all Journal
> J Clin Psychiatry. 1995 Oct;56(10):476-83.
>
> Affiliation
> Department of Psychiatry, University of Vermont College of Medicine, Burlington, USA.
>
> Abstract
> BACKGROUND: An association found between akathisia and iron deficiency led to the suggestion that iron supplementation might be a useful therapeutic intervention for patients with akathisia. There is, however, a body of literature on the abnormal deposition of iron in the brain in several degenerative diseases like Hallervorden-Spatz syndrome, Parkinson's disease, and Alzheimer's disease. Given the ability of neuroleptics to chelate iron and promote its deposition in the brain, we questioned whether peripheral measures of iron are an accurate reflection of central iron levels and thus whether there was a rationale for iron supplementation in akathisia.
>
> METHOD: A MEDLINE search for literature relating to iron and akathisia, tardive dyskinesia, and Parkinson's disease was carried out and critically reviewed.
>
> RESULTS: Evidence is presented for the ability of neuroleptics to chelate iron, mobilize it from peripheral stores, and deposit it in the basal ganglia. The effect of iron on dopaminergic receptor activity in brain and the potential role of iron in degenerative and neuroleptic-induced movement disorders are reviewed. The preponderance of the evidence shows a relationship between iron excess in the basal ganglia and the movement disorders. We found no studies that have examined the regulation of central levels of iron in patients with akathisia.
>
> CONCLUSION: The rationale for iron supplementation in the treatment of akathisia is relatively weak, and there are potentially adverse long-term consequences as outlined in our review. More research is required to directly measure the level of iron in the brain of patients with akathisia, e.g., using magnetic resonance imaging, before such therapeutic intervention can be recommended.
Posted by LostBoyinNCReturns on March 31, 2012, at 18:38:52
In reply to Re: Study: Iron supplement + antipsychotics don't mix, posted by LostBoyinNCReturns on March 31, 2012, at 11:05:27
I read this a lot more closely and it mentions anti-psychotics move iron and deposit it into the basal ganglia? And actually increases the chance of developing degenerative movement disorders?
Wow. Man, people on anti-psychotics have it so badly. The side effect profile of those drugs is absolutely horrible, elevated blood sugar for atypical APs, TD, EPS, interaction with iron supplements...the list goes on.
Glad my diagnosis is not schizophrenia, I feel bad for those whose dx is that.
Eric
>
> > Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence.
> >
> > AuthorsGold R, et al. Show all Journal
> > J Clin Psychiatry. 1995 Oct;56(10):476-83.
> >
> > Affiliation
> > Department of Psychiatry, University of Vermont College of Medicine, Burlington, USA.
> >
> > Abstract
> > BACKGROUND: An association found between akathisia and iron deficiency led to the suggestion that iron supplementation might be a useful therapeutic intervention for patients with akathisia. There is, however, a body of literature on the abnormal deposition of iron in the brain in several degenerative diseases like Hallervorden-Spatz syndrome, Parkinson's disease, and Alzheimer's disease. Given the ability of neuroleptics to chelate iron and promote its deposition in the brain, we questioned whether peripheral measures of iron are an accurate reflection of central iron levels and thus whether there was a rationale for iron supplementation in akathisia.
> >
> > METHOD: A MEDLINE search for literature relating to iron and akathisia, tardive dyskinesia, and Parkinson's disease was carried out and critically reviewed.
> >
> > RESULTS: Evidence is presented for the ability of neuroleptics to chelate iron, mobilize it from peripheral stores, and deposit it in the basal ganglia. The effect of iron on dopaminergic receptor activity in brain and the potential role of iron in degenerative and neuroleptic-induced movement disorders are reviewed. The preponderance of the evidence shows a relationship between iron excess in the basal ganglia and the movement disorders. We found no studies that have examined the regulation of central levels of iron in patients with akathisia.
> >
> > CONCLUSION: The rationale for iron supplementation in the treatment of akathisia is relatively weak, and there are potentially adverse long-term consequences as outlined in our review. More research is required to directly measure the level of iron in the brain of patients with akathisia, e.g., using magnetic resonance imaging, before such therapeutic intervention can be recommended.
>
>
Posted by emmanuel98 on March 31, 2012, at 19:23:04
In reply to Re: Study: Iron supplement + antipsychotics don't mix, posted by LostBoyinNCReturns on March 31, 2012, at 18:38:52
One thing that struck me is that this works for people with an iron deficiency. Iron supplements for those without a deficiency are quite dangerous. I had akathesia from too high a dose of perphenazine and found that benadryl, xanax and exercise all helped. Also cutting the dosage of trilafon.
Posted by Bob12 on April 2, 2012, at 13:55:22
In reply to Re: Study: Iron supplement + antipsychotics don't mix, posted by emmanuel98 on March 31, 2012, at 19:23:04
I am on Zyprexa 17.5 mg for around 11 years, and have been taking a centrum multivitamin for all this time. Does this mean I should discontinue the multivitamin?
Bob12
Posted by Novelagent on April 5, 2012, at 7:15:06
In reply to Re: Study: Iron supplement + antipsychotics don't mix, posted by LostBoyinNCReturns on March 31, 2012, at 17:38:52
Schizophrenia has not affected my life outside of a 2 week hospitalization and the day preceding that intake.I'm on Invega Sustenna monthly shots and that's it. No positive or negative symptoms. I think the reason people get worse symptoms With it have let their meds lapse, as each episode worsens prognosis. I don't mess around. Also, higher IQs fair better (more IQ to spare).
Schizophrenia ain't as bad as ADD...
> I read this a lot more closely and it mentions anti-psychotics move iron and deposit it into the basal ganglia? And actually increases the chance of developing degenerative movement disorders?
>
> Wow. Man, people on anti-psychotics have it so badly. The side effect profile of those drugs is absolutely horrible, elevated blood sugar for atypical APs, TD, EPS, interaction with iron supplements...the list goes on.
>
> Glad my diagnosis is not schizophrenia, I feel bad for those whose dx is that.
>
> Eric
> >
> > > Is there a rationale for iron supplementation in the treatment of akathisia? A review of the evidence.
> > >
> > > AuthorsGold R, et al. Show all Journal
> > > J Clin Psychiatry. 1995 Oct;56(10):476-83.
> > >
> > > Affiliation
> > > Department of Psychiatry, University of Vermont College of Medicine, Burlington, USA.
> > >
> > > Abstract
> > > BACKGROUND: An association found between akathisia and iron deficiency led to the suggestion that iron supplementation might be a useful therapeutic intervention for patients with akathisia. There is, however, a body of literature on the abnormal deposition of iron in the brain in several degenerative diseases like Hallervorden-Spatz syndrome, Parkinson's disease, and Alzheimer's disease. Given the ability of neuroleptics to chelate iron and promote its deposition in the brain, we questioned whether peripheral measures of iron are an accurate reflection of central iron levels and thus whether there was a rationale for iron supplementation in akathisia.
> > >
> > > METHOD: A MEDLINE search for literature relating to iron and akathisia, tardive dyskinesia, and Parkinson's disease was carried out and critically reviewed.
> > >
> > > RESULTS: Evidence is presented for the ability of neuroleptics to chelate iron, mobilize it from peripheral stores, and deposit it in the basal ganglia. The effect of iron on dopaminergic receptor activity in brain and the potential role of iron in degenerative and neuroleptic-induced movement disorders are reviewed. The preponderance of the evidence shows a relationship between iron excess in the basal ganglia and the movement disorders. We found no studies that have examined the regulation of central levels of iron in patients with akathisia.
> > >
> > > CONCLUSION: The rationale for iron supplementation in the treatment of akathisia is relatively weak, and there are potentially adverse long-term consequences as outlined in our review. More research is required to directly measure the level of iron in the brain of patients with akathisia, e.g., using magnetic resonance imaging, before such therapeutic intervention can be recommended.
> >
> >
>
>
Posted by Novelagent on April 5, 2012, at 7:18:48
In reply to Re: Study: Iron supplement + antipsychotics don't, posted by Bob12 on April 2, 2012, at 13:55:22
> I am on Zyprexa 17.5 mg for around 11 years, and have been taking a centrum multivitamin for all this time. Does this mean I should discontinue the multivitamin?
>
> Bob12Iron is not going to be in a multivitamin. That bottle has a label with print on it. When you're feeling bored sometime, consider reading it. : )
Posted by Bob12 on April 14, 2012, at 7:42:47
In reply to Re: Study: Iron supplement + antipsychotics don't, posted by Novelagent on April 5, 2012, at 7:18:48
Iron is in fact present in Centrum multivitamin. I suggest you read the label too.
Bob12
Posted by Alexei on April 21, 2012, at 9:20:28
In reply to Re: Study: Iron supplement + antipsychotics don't mix » LostBoyinNCReturns, posted by Novelagent on April 5, 2012, at 7:15:06
> Schizophrenia ain't as bad as ADD...By what logic do you make this statement?
This is the end of the thread.
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