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<p class="ltrs-br-ltr-br-title">Prolactin—A Biomarker for Antipsychotic Treatment Response?</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold">To the Editor:</span> Antipsychotic-induced hyperprolactinemia, due to blockade of D<span class="subscript">2</span> receptors in the tubulo-infundibular dopaminergic pathway,<span class="htm-cite"><a href="#ref1">1</a></span> has been examined predominantly from the perspectives of adverse effects.<span class="htm-cite"><a href="#ref2">2</a></span> Interestingly, the “neuroleptic threshold” construct conceptualizes the D<span class="subscript">2/3</span> occupancy to underlie the clinical efficacy of antipsychotics.<span class="htm-cite"><a href="#ref3">3</a></span> Antipsychotic-induced hyperprolactinemia, being a proxy indicator of D<span class="subscript">2</span> receptor occupancy of antipsychotics, is reported to be associated with clinical improvement in a short-term study.<span class="htm-cite"><a href="#ref4">4</a></span> Intriguingly, prolactin has even been hypothesized to mediate the adaptive effects of antipsychotics.<span class="htm-cite"><a href="#ref5">5</a></span> In this report, we describe association between hyperprolactinemia and clinical improvement during a 5-month treatment period.</p>
<p class="ltrs-br-ltr-br-body-text">&nbsp;</p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Method</span><span class="bold">.</span> Clinical records of 10 patients with <span class="italic">DSM-IV</span> schizophrenia (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD age<span class="thinspace"> </span>=<span class="thinspace"> </span>29.3<span class="thinspace"> </span>±<span class="thinspace"> </span>6.5 years; 9 women) attending the Metabolic Clinic in Psychiatry at the National Insitute of Mental Health &amp; Neurosciences (Bangalore, India) from 2008 to 2010 were examined in this study. Four of the patients were on monotherapy with risperidone, 3 were on combination treatment with risperidone and another antipsychotic (1 each with amisulpride, quetiapine, and chlorpromazine), 2 were on treatment with olanzapine alone, and 1 was on combination treatment with olanzapine and amisulpride. Baseline data were taken from the time of registration, and follow-up data were from their most recent visit. Pearson correlation test was applied between baseline serum prolactin level and follow-up Clinical Global Impressions–Improvement scale (CGI-I)<span class="htm-cite"><a href="#ref6">6</a></span> score and between baseline prolactin level and antipsychotic dose (chlorpromazine equivalent).<span class="htm-cite"><a href="#ref7">7</a>,<a href="#ref8">8</a></span></p>
<p class="ltrs-br-ltr-br-body-text"><span class="bold-italic">Results.</span> There was a significant negative correlation between baseline serum prolactin level (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD<span class="thinspace"> </span>=<span class="thinspace"> </span>102.0<span class="thinspace"> </span>±<span class="thinspace"> </span>51.6 ng/mL) and CGI-I score (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD<span class="thinspace"> </span>=<span class="thinspace"> </span>1.5<span class="thinspace"> </span>±<span class="thinspace"> </span>0.5) at follow-up (<span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.016; <span class="italic">r</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−0.731), ie, the higher the prolactin level, the lower the CGI-I score, indicating those who had a higher prolactin level at baseline had better improvement at follow-up. Serum prolactin level did not correlate significantly with the baseline antipsychotic dose (mean<span class="thinspace"> </span>±<span class="thinspace"> </span>SD<span class="thinspace"> </span>=<span class="thinspace"> </span>302.7<span class="thinspace"> </span>±<span class="thinspace"> </span>78.5 mg/d) (<span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.609; <span class="italic">r</span><span class="thinspace"> </span>=<span class="thinspace"> </span>−0.185). There was no significant difference between the antipsychotic dose at baseline (302.7<span class="thinspace"> </span>±<span class="thinspace"> </span>78.5 mg/d) and that at follow-up (267.8<span class="thinspace"> </span>±<span class="thinspace"> </span>127.3 mg/d) (<span class="italic">P</span><span class="thinspace"> </span>=<span class="thinspace"> </span>.468).</p>
<p class="ltrs-br-ltr-br-body-text">&nbsp;</p>
<p class="ltrs-br-ltr-br-body-text">Our findings lend further support to the possible association between serum prolactin level and clinical improvement with antipsychotics. Our findings are in accord with an earlier short-term study reporting association between hyperprolactinemia and clinical improvement.<span class="htm-cite"><a href="#ref4">4</a></span> Findings of our study can have potential clinical implication as prolactin elevation could serve as a proxy indicator of D<span class="subscript">2</span> receptor occupancy—the mechanism of action of antipsychotics.<span class="htm-cite"><a href="#ref3">3</a></span> Prolactin elevation is seen to occur rapidly after just a single parenteral or oral dose of antipsychotic.<span class="htm-cite"><a href="#ref9">9</a></span> Hence, it can be used to predict treatment response even before clinical improvement with an antipsychotic happens and may, thus, help in formulation of individualized therapy.</p>
<p class="ltrs-br-ltr-br-body-text">Though our sample size is modest, this observation is valuable, especially in the context of the paucity of similar studies. Retrospective design might also be considered a limitation; however, this method avoided the rater bias on CGI assessment. In summary, this report suggests a potential role for prolactin to be used as a biomarker for treatment response in schizophrenia, warranting further systematic evaluation.</p>
<p class="ltrs-br-ltr-br-references-head"><span class="smallcaps">References</span></p>
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<p class="ltrs-br-ltr-br-author"><span class="bold">Sri M. Agarwal, MBBS</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Naren P. Rao, MBBS, MD</span></p>
<p class="ltrs-br-ltr-br-author"><a href="mailto:docnaren@gmail.com" target="_blank">docnaren@gmail.com</a></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Kapil Jhamnani, MBBS</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Ganesan Venkatasubramanian, MBBS, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Rishikesh V. Behere, MBBS, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Shivarama Varambally, MBBS, MD</span></p>
<p class="ltrs-br-ltr-br-author"><span class="bold">Bangalore N. Gangadhar, MBBS, MD</span></p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Author affiliations:</span> Department of Psychiatry, The Metabolic Clinic in Psychiatry, National Institute of Mental Health &amp; Neurosciences (NIMHANS), Bangalore, India.</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">Previous presentation: </span>International Conference on Schizophrenia; October 22–24, 2010; Chennai, India.</p>
<p class="ltrs-br-ltr-br-endmatter-fieldnotes"><span class="bold-italic">Published online:</span> August 25, 2011 (<span class="doi">doi:10.4088/PCC.11l01155</span>).</p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">Prim Care Companion CNS Disord 2011;13(4):</span><span class="doi">doi:10.4088/PCC.11l01155</span></p>
<p class="ltrs-br-ltr-br-copyright-doi"><span class="italic">© Copyright 2011 Physicians Postgraduate Press, Inc.</span></p>
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