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<p class="ltrs-br-ltr-br-title">Akathisia Causing Secondary Severe Depression in a Cancer Patient</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold">To the Editor</span><span class="bold-italic">:</span> Akathisia is a common side effect of neuroleptics or dopamine D<span class="subscript">2</span> receptor antagonists in the treatment of schizophrenia. Dopamine D<span class="subscript">2</span> receptor antagonists are also used as antiemetic agents in cancer patients and can induce akathisia. However, akathisia in palliative care is often unrecognized by general physicians or oncologists.<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref2">2</a></span> Akathisia may cause patients severe distress, but a major depressive–like episode secondarily induced by antiemetics in a cancer patient has not been reported. We report a case of a breast cancer patient who suffered from a severe major depressive–like episode induced by akathisia.</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Case report.</span> In September 2009, Ms A, a 37-year-old woman, was referred to us by a surgeon for investigation of anxiety. She had undergone surgery for left breast cancer at 32 years of age. Since 2007, she has received radiation and chemotherapy for the treatment of metastases to the lungs and parasternal lymph nodes. To relieve pain, oxycodone tablets (5 mg/d) had been prescribed with prochlorperazine (5 mg/d) as an antiemetic agent for 6 months, and 5 weeks previously the dose of oxycodone had been increased to 10 mg/d due to increased breast pain in conjunction with the increased dose of prochlorperazine (10 mg/d). Despite her pain, her activities of daily living were maintained well and she was able to enjoy her life, in activities such as travel with her family. Two weeks before her presentation, she suddenly experienced restlessness of her limbs and anxiety, and she began to walk all day long. Insomnia and loss of appetite appeared. Her restlessness was quite burdensome, and she became severely depressed with suicidal ideation. She was unable to do anything other than walking and moving her limbs. She had no past history of psychiatric disorders, including depression and mania.</p>
<p class="ltrs-br-ltr-br-body-text">On our psychiatric examination, all 9 symptoms listed as diagnostic criteria for a major depressive episode in <span class="italic">DSM-IV-TR</span><span class="htm-cite"><a href="#ref3">3</a></span> were present. Her score on the 17-item Hamilton Depression Rating Scale (HDRS)<span class="htm-cite"><a href="#ref4">4</a></span> was 36. However, typical symptoms of akathisia such as restlessness, fidgety movement of the legs, and inability to sit or stand still were also observed. Neurologic examination revealed slight Parkinson’s syndrome, with disturbance of the gait including lack of arm swing and brachybasia, but without tremor or muscle rigidity. On the basis of the symptoms and their time course, we strongly suspected prochlorperazine-induced akathisia and substance-induced mood disorder (severe depression). We recommended that she discontinue prochlorperazine and gave her supportive psychotherapy without prescribing antidepressants since her severe depression was strongly suspected to have been triggered by neuroleptic-induced akathisia. Following discontinuation of prochlorperazine, her akathisia improved dramatically. One week later, her akathisia was only episodic and of short duration, rather than continuous. Her depression disappeared with recovery from akathisia (HDRS score<span class="thinspace"> </span>=<span class="thinspace"> </span>5).</p>
<p class="ltrs-br-ltr-br-body-text"> </p>
<p class="ltrs-br-ltr-br-body-text">Akathisia usually develops as an acute extrapyramidal sign within a few weeks of starting or raising the dose of a neuroleptic medication (<span class="italic">DSM-IV-TR</span>).<span class="htm-cite"><a href="#ref3">3</a></span> Although she had taken prochlorperazine for 6 months, an increase in the dose of prochlorperazine triggered akathisia. Akathisia is commonly observed in the treatment of schizophrenia with neuroleptics, but it is not well known that it can develop during palliative care of patients with antiemetic agents, such as prochlorperazine and metoclopramide, which block central D<span class="subscript">2</span> receptors. Prochlorperazine has a very high affinity for D<span class="subscript">2</span> receptors comparable to that of haloperidol<span class="htm-cite"><a href="#ref5">5</a></span> and is likely to induce akathisia and other extrapyramidal side effects.</p>
<p class="ltrs-br-ltr-br-body-text">Akathisia induced by D<span class="subscript">2</span>-blocking antiemetic agents is frequently unrecognized in cancer patients.<span class="htm-cite"><a href="#ref1">1</a>,<a href="#ref2">2</a></span> Half of 24 cancer patients receiving metoclopramide and prochlorperazine developed akathisia.<span class="htm-cite"><a href="#ref1">1</a></span> Twenty of 483 patients referred to a department of psychiatry developed akathisia from an antiemetic drug (80% of such patients took prochlorperazine).<span class="htm-cite"><a href="#ref2">2</a></span> Major depression is also highly prevalent in cancer patients.<span class="htm-cite"><a href="#ref6">6</a></span> However, most oncologists and general physicians may be unaware that antiemetic-induced akathisia can cause severe depression with suicidality resembling major depressive disorder. Although prochlorperazine is one of the first-line drugs for the treatment of emesis induced by chemotherapy and opioids and is useful in caring for cancer patients, physicians should recognize that it, as well as D<span class="subscript">2</span>-blocking antiemetic agents other than domperidone, may have pronounced side effects. Long-term use of prochlorperazine should be avoided, or domperidone, a peripherally acting D<span class="subscript">2</span> antagonist, should be substituted for it if possible.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
<p class="references-references-text-1-9"><a name="ref1"></a>1. Fleishman SB, Lavin MR, Sattler M, et al. Antiemetic-induced akathisia in cancer patients receiving chemotherapy. <span class="italic">Am J Psychiatry</span>. 1994;151(5):763–765. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8166321&dopt=Abstract">PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref2"></a>2. Kawanishi C, Onishi H, Kato D, et al. Unexpectedly high prevalence of akathisia in cancer patients. <span class="italic">Palliat Support Care</span>. 2007;5(4):351–354. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=18044412&dopt=Abstract">PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref3"></a>3. American Psychiatric Association. <span class="italic">Diagnostic and Statistical Manual of Mental Disorders</span>, Fourth Edition, Text Revision <span class="italic">(DSM-IV-TR)</span>. Washington, DC: American Psychiatric Association; 2000.</p>
<p class="references-references-text-1-9"><a name="ref4"></a>4. Williams JB. A structured interview guide for the Hamilton Depression Rating Scale. <span class="italic">Arch Gen Psychiatry</span>. 1988;45(8):742–747. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3395203&dopt=Abstract">PubMed</a></span></p>
<p class="references-references-text-1-9"><a name="ref5"></a>5. Leysen JE, Janssen PM, Schotte A, et al. Interaction of antipsychotic drugs with neurotransmitter receptor sites in vitro and in vivo in relation to pharmacological and clinical effects: role of 5HT<span class="subscript">2</span> receptors. <span class="italic">Psychopharmacology (Berl)</span>. 1993;112(suppl 1):S40–S54. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7530377&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1007/BF02245006">doi:10.1007/BF02245006</a></span></p>
<p class="references-references-text-1-9"><a name="ref6"></a>6. Berard RM, Boermeester F, Viljoen G. Depressive disorders in an out-patient oncology setting: prevalence, assessment, and management. <span class="italic">Psychooncology</span>. 1998;7(2):112–120. <span class="pubmed-crossref"><a href="
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9589509&dopt=Abstract">PubMed</a> <a href="
http://dx.doi.org/10.1002/(SICI)1099-1611(199803/04)7:2%3C112::AID-PON300%3E3.3.CO;2-N">doi:10.1002/(SICI)1099-1611(199803/04)7:2<112::AID-PON300>3.3.CO;2-N</a></span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Takeshi Inoue, MD, PhD</span></p>
<p class="ltrs-br-ltr-br-author"><a href="
mailto:tinoue@med.hokudai.ac.jp" target="_blank">
tinoue@med.hokudai.ac.jp</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Masato Takahashi, MD, PhD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Mitsuchika Hosoda, MD, PhD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Tsukasa Koyama, MD, PhD</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Author affiliations:</span> Department of Psychiatry (Drs Inoue and Koyama) and First Department of Surgery (Drs Takahashi and Hosoda), Hokkaido University Graduate School of Medicine, Sapporo, Japan.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Potential conflicts of interest:</span> None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Funding/support:</span> None reported.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Published online:</span> August 19, 2010 (<span class="doi">doi:10.4088/PCC.09l00935blu</span>).</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion J Clin Psychiatry 2010;12(4):e1</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2010 Physicians Postgraduate Press, Inc.</span></p>
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