Emotional Effects of Sertraline: Novel Findings Revealed by Meditation

Roger Walsh, MD, PhD Bruce Victor, MD and Robin Bitner, MD University of California, Irvine University of California, San Francisco

Use of selective serotonin reuptake inhibitors continues to increase, as does concern about previously unrecognized, subtle side effects and questions about whether these drugs produce effects on healthy subjects. The authors report novel emotional effects identified by an experienced, psychologically healthy meditator who is a psychiatrist and researcher. On a meditation retreat, the subject identified a specific profile of emotional changes related to sertraline use. In particular, cognitive abilities and the emotions of fear and anger seemed unaffected. However, the emotions of sadness, happiness, rapture, and love were dramatically reduced in intensity and duration.

Keywords: sertraline, meditation, emotion

In recent years, the use of selective serotonin reuptake inhibitors reduced measures of negative affect and hostility and increased (SSRIs) has increased dramatically, making them among the most scores on social affiliation in healthy subjects (Knutson et al., commonly prescribed medications in medical practice. This in- 1998). A third study found that paroxetine and sertraline induced crease reflects both pharmacological and social factors. In terms of impairment in measures of cognitive, attentional, and psychomotor pharmacology, compared to earlier antidepressant compounds, function in healthy, older adults, even though none of these sub- SSRIs have fewer side effects, lower lethality, and a broader jects complained of related difficulties (Sherman, 2002). Clearly, spectrum of action. Social factors include an increase in the ap- there is cause for concern about possible subtle psychological side parent incidence and severity of depression as well as increased effects. social acceptance of antidepressant therapy by both patients and A novel approach to investigating subtle effects of SSRIs is to clinicians (Borch-Jacobson, 2002; Jain & Jain, 2002; Kramer, utilize subjects with exceptional introspective abilities. Consider- 1993; Olfson et al., 2002; Pignarre, 2001). able evidence now supports classic claims that meditation practice However, there is growing concern that SSRIs may have pre- may significantly enhance perceptual capacities. Perceptual sensi- viously unrecognized, subtle side effects, such as apathy and tivity, discrimination, processing speed, and empathy all appear to cognitive blunting. The American Psychiatric Association Text- be enhanced, as measured by, for example, reaction time, evoked book of Psychiatry (Hales, Yudofsky, & Talbott, 1999) refers to potential, Rorschach, tachistoscopic, and phenomenological re- “apathy syndromes,” characterized by “loss of motivation, in- ports. These perceptual changes are associated with a wide variety creased passivity and feelings of lethargy and ‘flatness’” (p. 1038). of psychological, biological, and therapeutic effects, including More dramatic extensions of this phenomenon, such as a “frontal changes in dopamine activity (for reviews, see Kjaer et al., 2002; lobe” syndrome, have also been reported (Abel, Igbal, & Holzer, Murphy & Donovan, 1997; D. Shapiro & Walsh, 1984; S. Shapiro 1998; Garland & Baerg, 2001; Hoehn-Saric et al., 1991; Hoehn- et al., 2002; S. Shapiro & Walsh, 2003; Walsh, 2000; Walsh & Saric, Lipsey, & McLeod, 1990; Opler, Ramirez, & Lee, 1994). Vaughan, 1993; West, 1987). We therefore offer a case study of an Recent research has also examined whether these medications experienced meditator who reported intriguing effects of sertraline exert effects on people who are not suffering from Axis I diag- on meditation experiences and affect. noses. Goodwin (1997) expressed the belief that any drug that alters abnormal personality is likely to alter normal personality as Method

This document is copyrighted by the American Psychological Association or one of its allied publishers. American Psychological This document is copyrighted by the well. However, to date, the research data have been mixed. One This article is intended solely for the personal use of individual user and not to be disseminated broadly. study found no effects of fluoxetine on self- and observer-rated The Subject measures of mood, general well-being, or quality of life in healthy The subject, Roger Walsh, was a 51-year-old caucasian male trained in subjects (Gelfin, Gorfine, & Lerer, 1998). Conversely, paroxetine medicine, psychiatry, and neuroscience who had practiced meditation for over 20 years. That the subject had developed a degree of perceptual and introspective sensitivity is suggested by the amount of meditation practice, Roger Walsh, Department of Psychiatry and Human Behavior, College teachers’ evaluations, his phenomenological reports, and the results ob- of Medicine, University of California, Irvine; Bruce Victor, MD, Depart- tained when he was a subject in a study of meditators’ perception (Brown ment of Psychiatry, Medical School, University of California, San Fran- & Engler, 1986a, 1986b; Walsh, 1977, 1978). He was in good physical and cisco; Robin Bitner, MD, Department of Psychiatry, Langley Porter Psy- mental health, except for a diagnostically undefined gastric motility disor- chiatric Institute, University of California, San Francisco. der, for which SSRIs were prescribed. A trial of fluoxetine resulted in We thank Drs. Owen Wolkowitz, Shauna Shapiro, Lorena Hillman, and disabling side effects of lethargy, abulia, and amotivational syndrome. Frances Vaughan for their helpful comments on this article. He was subsequently switched to 50 mg sertraline daily and remained on For reprints and correspondence: Bruce Victor, MD, Department of this for a year. The only side effects identified during this time were mild Psychiatry, Medical School, University of California, 1819 Union Street, insomnia, occasional anorgasmia, and reduced frequency and intensity of San Francisco, CA 94143. E-mail: [email protected] peak experiences. Peak experiences are brief altered states of conscious-

134 EMOTIONAL EFFECTS OF SERTRALINE 135

ness marked by feelings of ecstatic affect and a transpersonal self-sense, subject was taking sertraline, they were dramatically less intense that is, a self-sense extending beyond the usual personal, egoic, and and less long lasting than in any previous retreat. somatic boundaries. Peak experiences can occur spontaneously in anyone Ceasing and recommencing sertraline provided further observa- but are especially common in psychologically healthy individuals and in tions. After the subject ceased all sertraline, the emotions of long-term meditators (Maslow, 1971; Alexander, Rainforth, & Gelderloos, sadness, happiness, rapture, and love slowly reverted to their usual 1991). intensity and patterns. At the end of 5 days, there was significant, though still partial, normalization. However, during those 5 days The Brahma Vihara Meditations the subject’s gastric motility disorder exacerbated significantly, and on the 5th day he resumed 50 mg sertraline per day. Over the The subject did a 3-week retreat to practice the Buddhist brahma vihara remaining 3 days of brahma vihara practice, the four emotions of meditations, 2,500-year-old practices that focus on transforming emotions sadness, happiness, rapture, and love once again regressed to less (Goleman, 1988; Tin, 1975; Walsh, 1999, 2000). The brahma vihara intense and less enduring profiles. The net result of this cessation practices employ the continuous recitation of appropriate phrases to culti- and recommencement of medication was a tidy, albeit inadvertent, vate emotional qualities, such as love and compassion. Done continuously three part ABA single-case study design, a design that is particu- over days or weeks, the effects can be dramatic. The desired emotions, such as love, may develop to remarkable degrees, as may accompanying emo- larly valuable for assessing intervention effects in single individ- tions, such as happiness and rapture,1 and related qualities, such as con- uals (Masters, Burish, Hollon, & Rim, 1987). centration and calm. In these meditative states, the mind is described as remarkably pliant or Discussion malleable. Just as a person trained in relaxation can rapidly elicit an experience of calm, so, too, an experienced brahma vihara meditator is Limitations of This Study said to develop “mental pliancy” and can quickly elicit specific mental qualities, such as those just described (Epstein, 1975; Nyanaponika, 1998; There are clearly significant limitations to this study. First, it Tin, 1975). was a single-case study using only subjective measures. Future studies would benefit from using multiple subjects and both subjective and objective measures. Second, the ABA design, though Results valuable, was suboptimal, as the 5-day washout B phase and the For the first 6 days of the retreat, the subject continued to take final C phase, in which sertraline was reintroduced, were both 50 mg sertraline daily. For the next 5 days, he reduced this to 25 relatively short. Third, the fact that the subject is a psychiatrist may mg as part of a preplanned gradual withdrawal to observe how the perhaps make his observations more clinically astute but also gastric motility disorder responded. During these initial 11 days (6 raises the possibility of expectancy effects. on 50 mg and 5 on 25 mg), he observed that the effects of the However, there are several factors that suggest that the observed brahma vihara meditations were very dramatically less marked changes were significantly more than expectancy effects. These than in previous retreats he had done of this kind. In particular, the include the dramatic nature and intensity of the changes and their emotional qualities of happiness, rapture, and love, which previ- specificity. In addition, the subject had not noticed any emotional ously had been intense to the point of ecstasy, were now far less effects during the previous year or on a previous retreat doing a intense and faded more rapidly than in the past. different kind of meditation and so was not expecting emotional After 11 days, the subject realized that this difference might be effects to emerge at this late stage. due to the sertraline. He therefore immediately began a systematic Despite these significant limitations, the study offers unique exploration of its subjective effects and, after a day, ceased taking opportunities and data. These include the rare—indeed, unique— the medication. This exploration made use of the mental pliancy— combination of observations by a mental health professional with the ability described above that brahma vihara meditations con- long-term introspective training, identification of a novel and fer—of eliciting certain mental qualities at will. highly specific profile of SSRI-induced emotional effects, and the A specific profile of medication effects on mental qualities and finding that these effects were observable only during a specific capacities was observed. There were no discernable effects on kind of intensive meditation practice. This document is copyrighted by the American Psychological Association or one of its allied publishers. American Psychological This document is copyrighted by the nonemotional factors. For example, when the attentional and cog- This article is intended solely for the personal use of individual user and not to be disseminated broadly. nitive factors of concentration, initial attention, and sustained Psychopharmacologic Implications attention2 were elicited, they appeared to arise to their normal degree and then to follow their usual pattern of diminishing slowly This report holds several implications. First, it suggests that over a matter of minutes. The same was true of the emotions of constrictive emotional side effects can begin at low doses, indeed, fear and anger. at what would be considered an appropriate “starting” dose of However, a very different intensity and time course were ob- sertraline. Second, this report demonstrates how subtle and diffi- served for the four emotions of sadness, happiness, rapture, and cult to detect these side effects can be, as the subject first identified love. When deliberately elicited, each of these emotions began to arise as usual and could be clearly experienced. However, within 1 Rapture is an intense joy or ecstasy associated with concentrated, clear a matter of seconds and before peaking, they simply disappeared awareness, accompanied by pleasurable somatic sensations and piloerec- and could no longer be felt. In particular, the three positive tion (goose bumps). emotions of happiness, rapture, and love are usually extremely 2 The classical Pali terms found in meditation texts for these mental strong and enduring during brahma vihara retreats, far more capacities are ekagatta (concentration), vitakka (initial attention), and powerful than at any other time. However, on this retreat, while the vicara (sustained attention). 136 WALSH, VICTOR, AND BITNER

the decline in affective range only while on a meditation retreat. tional effects became strikingly obvious. Only in retrospect did he Thus, although the subject did not experience the full frontal lobe recognize as a drug effect a slightly heightened sense of equanim- syndrome described in some articles, he did note a drastically ity during the previous year and Vipassana retreat. reduced ability to attain exceptionally positive and salutary emo- This equanimity was confirmed independently by two people. A tions and states of mind. Third, this article, therefore, corroborates meditation instructor spontaneously commented that the subject’s previous reports regarding affective constriction but extends pre- experiences seemed just like those of someone doing an equanim- vious findings by pointing to a specific profile of affective ity meditation practice. Likewise, the subject’s wife, herself a changes. psychologist, spontaneously retrospectively described the subject Fourth, the present report suggests that sertraline and perhaps as having been “more mellow and easier to get along with” while other SSRIs may inhibit some exceptionally positive and salutary he had been on sertraline. This suggests that family members may emotions and states of mind, such as those cultivated by contem- sometimes be more sensitive to subtle behavioral changes than are platives. Fifth, there is a disconcerting possibility that some of the the subjects themselves and that interviewing family members may inhibition may be chronic. In part because of his long-term med- be a valuable research strategy for detecting such changes. itation practice, the subject was used to periodically experiencing If the subject’s experiential and behavioral changes do reflect a highly valued peak experiences during daily life. These were drug-induced increase in equanimity—or what the psychiatrists reduced in frequency and intensity while he was taking sertraline, Zetzel (1970) and Kramer (1993), respectively, called affect tol- and this reduction seemed to continue, and only slowly recover, erance and experience tolerance—this would be consistent with a over a period of several years. recent study of meditators taking antidepressants who claimed that Sixth, because the subject was not suffering from an Axis I one of the drug’s most dramatic effects was to enhance equanim- mood or anxiety disorder, these observations corroborate reports ity. These reports of heightened equanimity, both in this article and that SSRIs may induce psychological effects in healthy individuals in the group study, suggest that an increase in equanimity might be (Knutson et al., 1998; Sherman, 2002). However, this report also a factor accounting for the remarkably broad-ranging therapeutic extends Knutson et al.’s findings to include more subtle negative benefits of SSRIs (Bitner, Hillman, Victor, & Walsh, 2003). changes as well as the positive ones they described. Furthermore, The subject’s initial failure to recognize drug-induced subjective the highly specific profile of emotions affected is consistent with changes is consistent with the growing concern that there may be the claim that these agents could provide researchers with power- a wide range of subliminal psychological side effects of pharma- ful tools for the ‘pharmacologic dissection’ of distinct phenome- cological agents that usually go unrecognized—for example, pos- nological aspects of normal personality (Knutson et al., 1998). sible effects of some cholesterol-lowering drugs on attention, The seventh pharmacological implication concerns meditators dexterity, and car accidents (Muldoon, 1997). Perhaps meditators needing antidepressants. There are now several million meditation and other introspectively trained subjects may be able to detect practitioners in the United States alone, and this population seems subtle side effects and alert researchers to variables warranting particularly resistant to using medications, in part because of systematic study. concerns about possible costs to their practice and in part because of lack of available information on such effects (Carr, 1999; Conclusion Epstein, 1993; Moon, 2001; Victor, 1996, 1999). The present study suggests that there may be possible costs but that they may perhaps Though limited by its single-case design, this report suggests a be limited to specific types of meditation. number of important possible implications. (a) Pharmaceuticals may induce a variety of usually subliminal side effects, (b) meditators may be able to recognize some of these and alert researchers Using Meditators for Psychopharmacological Research to them, and (c) different types of meditation may be differentially For much of the 20th century, introspection was anathema to effective in revealing these side effects. (d) SSRIs may have experimental psychology but essential to clinical psychology and effects—including affective constriction—on psychologically psychiatry. Within recent years, the balance has shifted, and in- healthy individuals, (e) may produce a specific profile of effects on trospection is increasingly recognized as a valuable, even essential, different affects, and (f) may limit the intensity not only of strong This document is copyrighted by the American Psychological Association or one of its allied publishers. American Psychological This document is copyrighted by the component of psychological and neuroscientific research (Flanna- negative emotions but of strong positive emotions also. These This article is intended solely for the personal use of individual user and not to be disseminated broadly. gan, 1991, 1997; Varela & Shear, 1999; Wallace, 2000). In addi- implications suggest that more sophisticated studies of meditation, it has been suggested that individuals trained in both science tors—such as double-blind, placebo-controlled designs employing and introspective disciplines, such as meditation or yoga, might both subjective and objective measures—are warranted to attempt prove especially valuable subjects (Tart, 1972, 1975; Wallace, to detect subtle psychological effects of pharmaceuticals. 2000). This study supports these ideas and also suggests that meditators may be valuable subjects for psychopharmacological References research. However, this study also suggests that the type of meditation Abel, L., Igbal, J. D., & Holzer, J. C. (1998). Paroxetine and amotivational syndrome. Brain Injury, 8, 721–722. may be crucial and that there may be a Drug ϫ Type of Meditation Alexander, C., Rainforth, M., & Gelderloos, P. (1991). Transcendental interaction. The subject had done a year of daily practice and a meditation, self actualization and psychological health: A conceptual 10-day retreat using a Buddhist awareness meditation (Vipassana) overview and statistical meta-analysis. Journal of Social Behavior and without at the time identifying any marked effects of sertraline. It Personality, 6, 189–249. was not until he did intensive brahma vihara meditation—a spe- Bitner, R., Hillman, L., Victor, B., & Walsh, R. (2003). Subjective effects cific emotion-inducing practice—in retreat that the drug’s emo- of antidepressants: A pilot study of the varieties of antidepressant- EMOTIONAL EFFECTS OF SERTRALINE 137

induced experiences in meditators. Journal of Nervous and Mental Moon, S. (2001, November). I want to tell you about coming apart. Disease, 191, 660–667. Shambhala Sun, 40–45. Borch-Jacobson, M. (2002, July 11). Psychotropicana. London Review of Muldoon, M. (1997, November 11). “Cholesterol lowering drugs may dull Books, 17–18. alertness,” New York Times, p. B13. Brown, D., & Engler, J. (1986a). The stages of mindfulness meditation: A Murphy, M., & Donovan, S. (1997). The physical and psychological effects validation study: Part II. Discussion. In K. Wilber, J. Engler, & D. of meditation (2nd ed.). Sebastopol, CA: Institute of Noetic Sciences. Brown (Eds.), Transformations of consciousness: Conventional and Nyanaponika, T. (1998). Abhidhamma studies: Buddhist exploration of contemplative perspectives on development (pp. 191–218). Boston: New consciousness and time. Somerville, MA: Wisdom Publications. Science Library/Shambhala. Olfson, M., Marcus, S., Druss, B., Elinson, L., Tanielien, T., & Pincus, H. Brown, D., & Engler, J. (1986b). The states of meditation in cross cultural (2002). National trends in the outpatient treatment of depression. Jour- perspectives. In K. Wilber, J. Engler, & D. Brown (Eds.), Transforma- nal of the American Medical Association, 287, 203–209. tions of consciousness: Conventional and contemplative perspectives on Opler, L. A., Ramirez, P. M., & Lee, S. (1994). Serotonergic agents and development (pp. 219–284). Boston: New Science Library/Shambhala. frontal lobe syndrome. Journal of Clinical Psychiatry, 55, 362–363. Carr, S. (1999). Meditation and medication in a personal tale of clinical Pignarre, P. (2001). Comment la de´pression est devenue une e´pide´mie. depression. Perspectives in Biology and Medicine, 43(1), 98–102. Paris: De´couverte [How depression became an epidemic]. Epstein, M. (1975). Buddhist psychology. Unpublished thesis, Department Shapiro, D., & Walsh, R. (Eds.). (1984). Meditation: Classic and contem- of Psychology and Social Relations, Harvard University. porary perspectives. New York: Aldine. Epstein, M. (1993, Fall). Awakening with Prozac: Pharmaceuticals and Shapiro, S., Schwartz, G., & Santerre, C. (2002). Meditation and positive practice. Tricycle, 30–34. psychology. In C. Snyder & S. Lopez (Eds.), Handbook of positive Flannagan, O. (1991). The science of mind (2nd ed.). Cambridge, MA: MIT psychology (pp. 632–645). New York: Oxford University Press. Press. Shapiro, S., & Walsh, R. (2003). An analysis of recent meditation research Flannagan, O. (1997). Prospects for a unified theory of consciousness or, and suggestions for future directions. Humanistic Psychologist, 31, what dreams are made of. In J. Cohen & J. Schooler (Eds.), Scientific 87–114. approaches to consciousness (pp. 405–422). Mahwah, NJ: Erlbaum. Sherman, C. (2002, April). SSRIs are associated with mild cognitive Garland, E. F., & Baerg. J. (2001). Amotivational syndrome associated impairment. Clinical Psychiatry News, 12. with selective serotonin re-uptake inhibitors in children and adolescents. Tart, C. (1972). States of consciousness and state specific sciences. Sci- Journal of Child and Adolescent Psychopharmacology, 11(2), 181–186. ence, 176, 1203–1210. Gelfin, Y., Gorfine, M., & Lerer, B. (1998). Effect of clinical doses of Tart, C. (1975). States of consciousness. New York: Dutton. fluoxetine on psychological variables in healthy volunteers. American Tin, P. M. (Trans.). (1975). The path of purity, being a translation of Journal of Psychiatry, 155, 290–292. Buddhagosa’s Visuddhimagga. London: Pali Text Society. Goleman, D. (1988). The meditative mind: The varieties of meditative Varela, F., & Shear, J. (Eds.). (1999). The view from within. Journal of experience. Los Angeles: J. P. Tarcher. Consciousness Studies, 6, 2. Goodwin, F. (1997, March 20). Studies differ on whether SSRIs affect Victor, B. (1996). Psychopharmacology and transpersonal psychiatry. In B. normal people. Psychiatric News, 18, 42. Scotton, A. Chenin, & J. Battista (Eds.), Textbook of transpersonal Hales, R., Yudofsky, S., & Talbott, J. (Eds.). (1999). American Psychiatric psychiatry and psychology (pp. 327–334). New York: Basic Books. Association textbook of psychiatry (2nd ed.). Washington, DC: Ameri- Victor, B. (1999). Transpersonal psychiatry and psychopharmacology. can Psychiatric Association. Psychiatric Annals, 32, 327–334. Hoehn-Saric, R., Harris, G. J., Pearlson, D., Cox, C. S., Macklin, S. R., & Wallace, A. (2000). The taboo of subjectivity. New York: Oxford Univer- Camargo, E. E. (1991). A fluoxetine-induced frontal lobe syndrome in sity Press. an obsessive compulsive patient. Journal of Clinical Psychiatry, 52(2), Walsh, R. (1977). Initial meditative experiences: Part I. Journal of 131–133. Transpersonal Psychology, 9, 151–192. Hoehn-Saric, R., Lipsey, J. R., & McLeod, D. R. (1990). Apathy and Walsh, R. (1978). Initial meditative experiences: Part II. Journal of indifference in patients on fluvoxamine and fluoxetine. Journal of Clin- Transpersonal Psychology, 10, 1–28. ical Psychopharmacology, 10, 343–345. Walsh, R. (1999). Essential spirituality: The seven central practices. New Jain, R., & Jain, S. (2002, June). Serotonin and norepinephrine: Are two York: Wiley. better than one? Psychiatric Times, 65–68. Walsh, R. (2000). Asian psychotherapies. In D. Wedding & R. Corsini Kjaer, T., Bertelson, C., Picini, P., Brooks, D., Alving, J., & Lou, H. (Eds.), Current psychotherapies (6th ed., pp. 409–444). Itasca, IL: (2002). Increased dopamine tone during meditation-induced change of Peacock.

This document is copyrighted by the American Psychological Association or one of its allied publishers. American Psychological This document is copyrighted by the consciousness. Cognitive Brain Research, 13, 255–259. Walsh, R., & Vaughan, F. (Eds.). (1993). Paths beyond ego. New York:

This article is intended solely for the personal use of individual user and not to be disseminated broadly. Knutson, B., Wolkowitz, O., Cole, S., Chan, T., Moore, E., Johnson, R., et Tarcher/Putnam. al. (1998). Selective alteration of personality and social behavior by West, M. (Ed.). (1987). The psychology of meditation. Oxford, England: serotonergic intervention. American Journal of Psychiatry, 155, 373– Clarendon Press. 379. Zetzel, E. (1970). The capacity for emotional growth. New York: Interna- Kramer, P. (1993). Listening to Prozac. New York: Penguin. tional University Press. Maslow, A. (1971). The farther reaches of human nature. New York: Viking. Masters, J., Burish, T., Hollon, S., & Rim, D. (1987). Behavior therapy: Received August 16, 2003 Techniques and empirical findings (2nd ed.). San Diego, CA: Harcourt, Revision received December 10, 2004 Brace, Jovanovich. Accepted December 28, 2004 Ⅲ