Journal of Affective Disorders 49 (1998) 141–144

Brief report

The SSRI antidepressants: Exploring their ‘‘other’’ possibleproperties

a , b a*William Andrews , Gordon Parker , Elaine BarrettaPsychiatry Unit, Prince of Wales Hospital, Sydney, Australia

bSchool of Psychiatry, University of New South Wales, Sydney, Australia

Accepted 21 November 1997

Abstract

Background: Anecdotal reports suggest that the SSRIs may have important properties in addition to their antidepressanteffects, possibly modifying mediating variables that dispose to and maintain depression. This preliminary study seeks toidentify any such potential variables. Methods: Fifty three subjects who had reported substantial general benefit to theirclinician after treatment with an SSRI were requested to retrospectively rate change across a range of constructs assessed byquestionnaire. Results: Differential effects were identified. Irritability, trait depression, worry and neuroticism scores showedthe most marked improvement, with cognitive style components also showing significant positive change. Equallyimportantly, there was no evidence of a positive response bias across all constructs. Conclusion: We suggest that the SSRIsmay act as ‘‘antiworry’’ agents and reduce irritability, neuroticism and dysfunctional attributions. Limitations: Our study wasretrospective and relied on self-report by volunteer patients who had been previously depressed. The study design cannotexclude the possibility that improvement reported on a number of measures may have been due to the amelioration ofresidual depression. Clinical relevance: The SSRIs, recognised as having antidepressant and anti-obsessional properties, mayalso have the capacity to lower irritability, worrying and neuroticism. This capacity could be useful per se but may, inaddition, reduce the occurrence and duration of depressive episodes, particularly by reducing ‘‘anxious worrying’’. 1998Elsevier Science B.V.

Keywords: Depression; SSRI; Antidepressants; Treatment

1. Introduction to report feeling ‘‘different’’ while continuing to takean SSRI following recovery from depression. For

The selective serotonin reuptake inhibitors (SSRIs) example, we have had patients report being ‘‘morehave been accepted as effective antidepressant enabled’’, ‘‘worrying less’’, or ‘‘feeling care-less’’agents. In addition, it is not uncommon for patients rather than ‘‘careless’’, being ‘‘less irritable,’’ and

with many describing depressive episodes to be less*Corresponding author. frequent and/or more transient. Anecdotally, most

0165-0327/98/$19.00 1998 Elsevier Science B.V. All rights reserved.PII S0165-0327( 97 )00203-6

142 W. Andrews et al. / Journal of Affective Disorders 49 (1998) 141 –144

observers appear to view such reports as simply items and details of SSRI use. Secondly, to providereflecting the remission of long-standing, smoulder- subjective impressions of both positive and negativeing, mild depression, so that the patient is truly effects of having taken an SSRI. Thirdly, theyeuthymic and merely describing their innate non- completed a structured questionnaire which askeddepressed state. them to consider how they were generally over the

We suspect an alternative phenomenon in a num- years (ie when not depressed and before taking anber of patients – that the SSRIs modify at-risk or SSRI), and to note changes since taking an SSRI.mediating variables that may both predispose to and Items were scored on a five-point scale from 2 2sustain depression. As the SSRIs have been reported (much more) through 0 (no change) to 2 (much less).to be of benefit to those with panic disorder (Oeh- The null hypothesis posed a mean score of 0.rberg et al., 1995), obsessive-compulsive disorder Regrettably, we did not inquire about duration of(Boyer et al., 1991) and dysthymia (Ravindran et al., SSRI treatment or polarity status.1994), candidate variables could include high trait The 209 item questionnaire consisted of itemsanxiety, ‘‘neuroticism’’ and a cognitive style prone presented in random order drawn from seven mea-to worrying. In this study we seek to identify any sures:such key variables, both to clarify this potentialbroader action of the SSRIs, and to assist design of 1. The NEO Five Factor Inventory (Costa andan intervention study which will target modification McCrae, 1978) which measures five major dimen-of any such constructs. The ideal design would be to sions of personality: (i) Neuroticism – a measurestudy a large sample of subjects prospectively (i.e. of sensitivity and emotional instability; (ii) Ex-before and after any prescription of an SSRI) and troversion-measuring outgoing, active and high-ensure that all candidate mediating variables are spirited characteristics, together with a preferenceassessed independently of both severity of baseline for company; (iii) Openness-assessing opennessmood state and subsequent improvement in mood to experience, broad interests and a rich imagina-state, to ensure that results are not confounded by tion; (iv) Agreeableness-assessing the tendency tostate effects of a depressed mood. be good-natured, co-operative and eager to avoid

We undertook an alternative initial study, seeking conflict; and (v) Conscientiousness-measuring or-to identify the likely candidate variables, recruiting ganisation, high standards and keenness topatients who reported substantive benefits apparently achieve goals.distinct from classical antidepressant effects, and 2. The Dysfunctional Attitude Scale (DAS; Weis-asking them to rate perceived changes retrospectively sman and Beck, 1978), which assesses ‘‘dysfunc-on a range of parameters. tional attitudes’’ and attributions, developed from

Beck’s explication of cognitive styles predispos-ing to depression.

2. Methods 3. The Automatic Thoughts Questionnaire (ATQ;Hollon and Kendall, 1980) which assesses fre-

2.1. Subjects and assessment procedure quency and severity of depression-related cogni-tions.

We invited clinicians at our hospitals to assist and, 4. The EPQ-N Scale (Eysenck and Eysenck, 1978),via a college journal, other Australian psychiatrists. with that neuroticism subscale of the larger EPQRespondents were invited to contribute patients who assessing instability under stress and strong emo-reported obtaining benefits from the SSRIs that went tional arousability.beyond alleviation of depression. Self-report ques- 5. The Costello-Comrey Depression and Anxietytionnaires and explanatory forms were distributed by Scales (Costello and Comrey, 1967), designed tothe participating psychiatrists to relevant patients for measure ‘‘trait’’ rather than ‘‘state’’ anxiety andcompletion. Data were collected anonymously and depression.results pooled for analysis. 6. The Locus of Control of Behaviour Scale (Craig

Subjects were first asked to complete demographic et al., 1984), assessing the extent to which events

W. Andrews et al. / Journal of Affective Disorders 49 (1998) 141 –144 143

are viewed as being a consequence of one’s own Table 1. Mean improvement (% change) is reported,behaviour and therefore potentially under person- with measures ranked by degree of improvement.al control (i.e. ‘‘internal locus’’). The greatest decreases were reported in irritability,

7. The Penn State Worry Questionnaire (Meyer et trait depression, worry and neuroticism, with cogni-al., 1990), which assesses ‘‘the trait of worry’’. tive style (as measured by the ATQ and DAS) also

8. In addition, a single ‘‘irritability’’ item was showing substantive change. Changes in trait anxietyincluded to respect clinical reports of SSRI medi- and locus of control of behaviour were less marked.cation being associated with less irritability. Some measures (eg. NEO extroversion, NEO open-

ness) showed minimal change. Such variability (ofdistinct to minimal change) suggests that change

3. Results scores were not simply driven by a generalisedresponse bias.

The sample consisted of 53 subjects (28 female,25 male) who returned completed questionnaires.Their mean age was 44 (range 23–74 years). Thirty 4. Discussionsubjects had received fluoxetine (mean dose 5 31mg/day), 18 sertraline (mean dose 5 101 mg/day) While the SSRIs were initially introduced asand 13 paroxetine (mean dose 5 20 mg/day). Eight antidepressants and have subsequently found a rolesubjects had received two SSRIs. in the treatment of panic disorder and obsessive-

Of the 48 (91% of sample) who provided unstruc- compulsive disorder, their effectiveness has yet to betured subjective comments about improvements since established in the treatment of what can be broadlytaking an SSRI, the most common reports were: conceptualised as ‘‘neurosis’’. Brief depressive epi-increased tolerance or control of daily stressors (n 5 sodes are an ubiquitous human experience, while14), reduced anxiety or tension (n 5 10), decreased clinical depression differs by being more severe andworrying (n 5 9), improved concentration (n 5 9), generally lasting longer. It may be that many whoand increased self-confidence (n 5 9). Of the 38 develop clinical depression lack those mechanisms(72% of sample) who reported negative effects of possessed by most people that facilitate such sponta-SSRIs on their general functioning, the most com- neous remission. Thus, ‘‘clinical depression’’ may bemon reports were: tiredness (n 5 14), and loss of induced and maintained by a cognitive style char-sexual desire and/or anorgasmia (n 5 14). acterised by anxious worrying that prevents the

Percentage changes on the scales and constructs individual from obtaining emotional ‘‘distance’’ fromassessed in the 209 item questionnaire are given in any depressogenic stressor. Our study results suggest

Table 1Mean improvement on questionnaire scores

Instrument Direction of Mean changechange

Irritability item Decrease 41.5%Costello-Comrey Trait Depression Decrease 39.1%Penn State Worry Questionnaire Decrease 38.0%NEO Neuroticism Decrease 34.4%Automatic Thoughts Questionnaire Decrease 31.2%EPQ Neuroticism Decrease 30.0%Dysfunctional Attitudes Scale Decrease 29.2%Costello-Comrey Trait Anxiety Decrease 27.7%Locus of Control of Behaviour More internal 24.9%NEO Agreeableness Increase 22.0%NEO Conscientiousness Increase 18.3%NEO Extroversion Increase 12.5%

144 W. Andrews et al. / Journal of Affective Disorders 49 (1998) 141 –144

that SSRIs may act as ‘‘antiworry’’ agents, and A.S. Williams. In addition, we thank the NHMRCdecrease irritability, neuroticism, and dysfunctional (Program Grant 953208), as well as Mrs K. Eyersattributions, which in turn may impact on the onset and Mrs C. Taylor from the Mood Disorders Unit,and maintenance of depression. Such an effect could Prince Henry Hospital, for study assistance.be another example of how a biological interventioncan positively influence psychological surface‘‘markers’’ in depressed subjects, akin to the exam- Referencesple in this journal by Baving et al. (1997) whichreported an impact of sleep deprivation on negative Baving, L., Maes, M., Bohus, M. et al., 1997. Can negative

self-schemas in depressives be altered through sleep depriva-self-schemas.tion?. J. Affect. Disord. 42, 93–101.Our study is clearly preliminary, being retrospec-

Boyer, W.F., McFadden, G.A., Feighner, J.P., 1991. The efficacytive, relying on a (self-selected) volunteer sample of selective serotonin reuptake inhibitors in anxiety andand involving only small numbers. We have some obsessive-compulsive disorder. In: Boyer, W., Feighner, J.confidence that sample members did not merely (Eds.), Selective Serotonin Re-uptake Inhibitors. John Wiley,

Chichester, pp. 109–118.complete the inventory driven by a positive responseCosta, P.T., McCrae, R.R., 1978. NEO Five Factor Inventory,bias (whether from lifting of depression or personali-

Form S. Psychological Assessment Resources Inc., Florida.ty variables) as their spontaneous responses revealed Costello, C.G., Comrey, A.L., 1967. Scales for measuring depres-a high incidence of adverse SSRI effects in the sion and anxiety. J. Psychol. 66, 303–313.context of reporting overall benefit. Thus, tiredness Craig, A.R., Franklin, J.A., Andrews, G., 1984. A scale to

measure locus of control of behaviour. Br. J. Med. Psychol. 57,and sexual difficulties were noted by over a quarter173–180.of the sample, when lifting of depression would

Eysenck, H.J., Eysenck, S.B.G., 1978. Manual of the Eysenckgenerally be expected to be associated with de- Personality Questionnaire. Educational and Industrial Testingcreased tiredness and increased sexual desire. Addi- Service, San Diego.tionally, change scores showed a wide scatter with Hollon, S.D., Kendall, P.C., 1980. Cognitive self-statements in

depression: development of an Automatic Thoughts Ques-more temperament-based constructs such as ex-tionnaire. Cogn. Ther. Res. 4, 383–395.troversion displaying minimal change.

Meyer, T.J., Miller, M.L., Metzger, R.L., Borkovec, T.D., 1990.Despite design limitations, we suggest that our Development and validation of the Penn State Worry Ques-

study assists identification of likely candidate tionnaire. Behav. Res. Ther. 28, 487–495.mediating variables modifiable by the SSRIs, which Oehrberg, S., Christiansen, P.E., Behnke, K. et al., 1995. Parox-

etine in the treatment of panic disorder. Br. J. Psychiatry 167,may both dispose to, and maintain depression. These374–379.are worthy of systematic examination in a prospec-

Ravindran, A.V., Bialik, R.J., Lapierre, M.D., 1994. Therapeutictive study to determine whether reported ‘‘personali- efficacy of specific serotonin reuptake inhibitors (SSRIs) inty’’ changes while on SSRIs represent amelioration dysthymia. Can. J. Psychiatry 39, 21–26.of long-standing depression, or the modification of Weissman, A.N., Beck, A.T., 1978. Development and validation

of the Dysfunctional Attitude Scale: A preliminary inves-vulnerability factors to depression.tigation. Paper presented at the American Educational ResearchAssociation, Toronto, March, 1978.

Acknowledgements

Study subjects were recruited by the authors andby Drs P. Birch, R. Field, B. Kimbell, I. Petroff and