Physiological Psychology

Vassar College

April 17, 2001

Trichotillomania falls into the category of impulse-control disorders not elsewhere classified in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (1994). The most distinguishing of the five diagnostic criteria set forth by the manual are recurrent pulling out of one's hair resulting in noticeable hair loss, an increasing sense of tension immediately before pulling out the hair or when attempting to resist the urge, and pleasure, gratification, or relief when pulling out the hair (DSM-IV 1994). The prevalence of trichotillomania, based on recent college surveys, is between 1% and 2%. In adults, trichotillomania appears to be much more prevalent among females than among males (DSM-IV 1994). This ratio may not reflect the true ratio but rather differences in seeking treatment based on cultural or gender-based attitudes regarding appearance (DSM-IV 1994). In the past, trichotillomania was considered a form of obsessive compulsive disorder (Ninan et al 1998), but the repetitive behavior of trichotillomania is now distinguished from the compulsion typical of obsessive compulsive disorder in which repetitive behaviors are performed in response to an obsession, or according to rigid rules (DSM-IV 1994). Trichotillomania also bears similarities to habit disorders such as onychophagia, nail biting, and skin picking (Ninan et al 1998). Some patients report feeling an itchlike sensation or a tingling on the site of the pulling, which is eased by the behavior (DSM-IV 1994) and which patients report as driving the motor-pulling response (Ninan et al 1998). This experience is similar to Tourette syndrome, in which somatosensory urges seem to drive motor tics; furthermore, certain neurological similarities have been observed between these conditions (Ninan et al 1998). Considering the difficulty in classifying this disorder, successful treatment is often elusive. Pharmaceutical treatment options draw from what has been successful in treating obsessive compulsive disorder and anxiety. Literature regarding pharmaceutical treatment of trichotillomania is mixed with regard to the success of drug therapy; however, despite individual successes in case studies, no one drug treatment has been demonstrated as being reliably effective treatment.

Despite methodological problems, case studies often report successful short-term treatment of trichotillomania, usually using drugs or drug combinations that are less traditional in the treatment of the disorder. The successful treatment of trichotillomania in case studies usually occurs in individuals for whom trichotillomania is comorbid with another disorder. It is important to note that comorbidity of trichotillomania with affective and anxiety disorders appears to be a rule rather than an exception, leading to the question of whether hair pulling ought to be considered both as a symptom present in multiple disorders and as a separate syndrome (Ninan et al 1998). An important question in this debate is to what extent is hair pulling alleviated when the comorbid condition is successfully treated (Ninan et al 1998). Pornnoppadol and Todd (1999) report a case study of an adolescent girl suffering from trichotillomania comorbid with bipolar affective disorder. Neither treatment with fluvoxamine nor paroxetine was successful (Pornnoppadol & Todd 1999). In fact, paroxetine, an antidepressant that is thought to have its effect by inhibiting the neuronal uptake of serotonin (PDR 1999), worsened the patient's mood lability and increased both aggressive outbursts and her hair pulling (Pornnoppadol & Todd 1999). Consultation at Pornnoppadol and Todd's clinic led to diagnosis of trichotillomania comorbid with bipolar affective disorder and she was started on lithium monotherapy (Pornnoppadol & Todd 1999). Lithium carbonate is indicated for treatment of manic episodes of manic-depressive illness; maintenance therapy prevents or lessens subsequent episodes (PRD: 1999). Mania typical presents itself as motor hyperactivity, reduced need for sleep, grandiosity, elation, poor judgment and aggressiveness (PDR 1999). The specific biochemical mechanism of lithium action is not known, although it has been shown to alter sodium transport in nerve and muscle cells (PDR 1999). Most patients on maintenance therapy are stabilized on 900 mg per day (PDR 1999), the dosage on which this patient was started (Pornnoppadol & Todd 1999). Within eight weeks of beginning treatment, both her mood symptoms and hair-pulling behavior significantly decreased (Pornnoppadol & Todd 1999). This is the first known case of trichotillomania comorbid with bipolar affective disorder in a child or adolescent (Pornnoppadol & Todd 1999). The response of trichotillomania in this comorbid case replicates similar findings of lithium treatment for simple trichotillomania (Pornnoppadol & Todd 1999). The authors recommend that psychiatrists consider lithium as a treatment option for patients with trichotillomania, especially those who demonstrate mood lability, have a family history for mood disorder, or both.

Another study (Reid 1992) reports a case of a woman presenting with generalized anxiety disorder comorbid with trichotillomania, who was successfully treated with buspirone. Buspirone is an anti-anxiety agent; it is indicated for the management of anxiety disorders or the shorter-term relief of the symptoms of anxiety (PDR 1999). Its mechanism of action is unknown; however it has been shown to have a high affinity for serotonin receptors and a moderate affinity for brain D2-dopamine receptors (PDR 1999). A dosage of between twenty and thirty mg per day is commonly employed in clinical trials (PDR 1999). The patient in this study started on a regimen of buspirone, thirty mg per day (Reid 1992). Within four weeks, the trichotillomania went into complete remission (Reid 1992). A significant alleviation of anxiety symptoms was also recorded (Reid 1992).

More common than bipolar disorder or generalized anxiety disorder comorbid with trichotillomania, is obsessive compulsive disorder comorbid with trichotillomania, most likely because they are probably from the same spectrum of disorders. Fluoxetine is a common treatment for obsessive compulsive disorder, often quite successfully. However, it is less successful in the treatment of trichotillomania. Fluoxetine is an antidepressant with anti-obsessive-compulsive and anti-bulimic properties (PDR 1999). Its actions are presumed to be linked to its inhibition of central nervous system neuronal uptake of serotonin; it blocks the uptake of serotonin into human platelets (PDR 1999). Potenza et al (1998) report a case study in which a woman presenting with obsessive compulsive disorder and trichotillomania was successfully treated with fluoxetine augmented with olanzapine. The initial treatment with fluoxetine effectively reduced depressive and obsessive-compulsive symptoms, but had no effect on the hair pulling (Potenza et al 1998). A trial with risperidone was associated with a significant decrease in hair pulling, but the patient developed intolerable side effects, hyperprolactinemia (Potenza et al 1998). Given olanzapine's lower propensity to alter prolactin secretion and the effectiveness of risperidone in combination with fluoxetine, an open-label trial of olanzapine addition was performed (Potenza et al 1998). Olanzapine is an anti-psychotic agent; like other anti-psychotics, its mechanism of action is unknown, but it is thought to be mediated through a combination of dopamine and serotonin type two antagonism (PDR 1999). Some clinical data suggest possible pharmacodynamics and/or pharmacokinetic interaction between selective serotonin reuptake inhibitors and anti-psychotics (PDR 1999). A significant decrease in hair pulling occurred following the olanzapine augmentation (Potenza et al 1998). Typically, the initial dosage is five to ten mg per day, with a target dose of ten mg per day within several days (PDR 1999). Anti-psychotic efficacy has been demonstrated in a dose range of ten to fifteen mg per day (PDR 1999). In this trial, at a dose of ten mg per day, sedation was reported. At a reduced olanzapine dose, two and a half mg per day, the only reported side effects were undesired weight gain (Potenza et al 1998). Symptoms of galactorhea were denied (Potenza et al 1998). This finding indicates a need for larger placebo-controlled, double-blind trials to study olanzapine augmentation in selective serotonin reuptake inhibitor-refractory trichotillomania.

Sunkureddi and Markovitz (1993), report another case study of a woman with a history of trichotillomania, dysthymia, and obsessive-compulsive disorder. After fluoxetine was abandoned due to side effects and both clomipramine and augmentation of clomipramine with buspirone failed, trazodone was begun at 200 mg per day (Sunkureddi & Markovitz 1993). Trazodone is an antidepressant whose action is not fully understood (PDR 1999). In non-human animals, trazodone selectively inhibits serotonin uptake by brain synaptosomes and potentiate, the behavior changes induced by the serotonin precursor, 5-hydroxytryptophan (PDR 1999). A typical initial dose is 150 mg per day in divided doses and the maximum dose for outpatients should not exceed 400 mg per day in divided doses (PDR 1999). In this study, trazodone was administered at 200 mg per day (Sunkureddi & Markovitz 1993). When using trazodone, as typically indicated, symptomatic relief may be seen during the first week (PDR 1999). Optimal antidepressant effects are typically evident within two weeks; however, 25% of those who respond require more than two weeks, up to four weeks, of drug administration (PDR 1999). In this study, the symptoms of trichotillomania began to improve within two weeks and by six weeks the trichotillomania and dysthymia had resolved (Sunkureddi & Markovitz 1993). The trichotillomania was still in remission at seven months, and obsessive-compulsive behaviors decreased (Sunkureddi & Markovitz 1993).

One case study reports successful treatment in an individual for whom trichotillomania was not comorbid with another disorder. As evident even in some the case studies above, fluoxetine, or any drug therapy, is not dependably successful as treatment for trichotillomania. Reid (1994) reports a case study of a man with trichotillomania who did not experience any decrease in hair pulling after trial of various selective serotonin reuptake inhibitors, fluoxetine and clomipramine. Paroxetine is an antidepressant also indicated in the treatment of obsessive compulsive disorder and panic disorder (PDR 1999). The antidepressant action of paroxetine and its efficacy in treatment of obsessive compulsive disorder and panic disorder is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from inhibition of neuronal reuptake of serotonin; studies show that paroxetine blocks uptake of serotonin into human platelets (PDR 1999). Treatment with paroxetine, forty mg per day, which is the recommended dosage for obsessive compulsive disorder (PDR 1999), brought significant alleviation of pulling within one month (Reid 1994). Continued treatment produced sustained results (Reid 1994). Paroxetine has the most potent inhibition of serotonin reuptake and desensitizes the terminal serotonin autoreceptors (Reid 1994). These attributes offer a possible explanation of paroxetine's role in the result of treatment in this case.

The successes of this and the other studies discussed above provide interesting information that may have implications in research on trichotillomania. However, given the very nature of case studies, no conclusions can be drawn without further research. The sample size of a case study is one, which significantly limits how much, if any, of the findings can be generalized to a population. Furthermore, these trials were not double-blind, placebo controlled studies, which limits how much causality can be inferred in the results. One cannot conclude whether the successes in treatment were due to the medication or to a placebo effect, in which improvement occurs because the patient knows the expected effects of the treatment and/or because the patient is receiving individual attention from a doctor. However, the successes of these case studies do justify further research on the efficacy of these drug therapies in the treatment of trichotillomania.

More traditional experimental techniques, such as clinical trials and controlled, double-blind studies, usually fail to find significant improvement in hair-pulling behavior. Most of the studies target fluoxetine in the treatment of trichotillomania; one open clinical trial did find some success in such treatment. The initial dosage for obsessive compulsive disorder is typically twenty mg per day (PDR 1999). A dose range of between twenty and sixty mg is recommended; eighty mg have been well tolerated in open studies of obsessive compulsive disorder, but dosage should not exceed eighty mg (PDR 1999). Koran et al (1992) report a study in which thirteen participants, of the original seventeen, completed an eight to twelve week open trial of fluoxetine, of up to eighty mg per day. None of the patients had obsessive-compulsive disorder or major depression (Koran et al 1992). The authors used the compulsions subscale of the Yale-Brown Obsessive-Compulsive Scale to rate patients' hair-pulling behavior. The thirteen participants' mean Yale-Brown Obsessive-Compulsive Scale score decreased significantly from 10.15 at baseline to 5.92 at the last visit (Koran et al 1992). Of these thirteen participants, five experienced a 50% or greater decrease in their pulling; four experienced between a 25% and 50% decrease (Koran et al 1992). Three of the patients stopped pulling entirely (Koran et al 1992). Of the patients who dropped out of the study, three discontinued treatment due to side effects and one insisted on early use of behavior therapy (Koran et al 1992). Common side effects of fluoxetine include anxiety and insomnia and altered weight and appetite. Despite the apparent success of fluoxetine in this study, the methodological problem with this study is a flaw of open clinical trials in general, that is that it lacks a control group and therefore, like case studies, cannot make valid conclusions about causality.

Although fluoxetine was successful in the above trial, more controlled studies of fluoxetine have failed to find significant effects. In their placebo-controlled, double-blind crossover study of fluoxetine, Christenson et al (1991) tried to classify trichotillomania based on whether it responds to fluoxetine. Their hypothesis was that if trichotillomania were a type of obsessive compulsive disorder, as some studies propose, then the anti-obsessional agent, fluoxetine would be useful in treating this disorder. To test the efficacy of fluoxetine in the treatment of trichotillomania, the authors recruited twenty-one adult chronic hair-pullers for an eighteen-week placebo-controlled, double-blind crossover study of fluoxetine, in doses up to eighty mg per day. Subjects were randomly assigned in double-blind fashion, neither the patient nor the administering experimenter knows whether the patient is in the fluoxetine or placebo group, to six-week trials of either fluoxetine or the placebo followed by a five-week washout period before crossover to the other treatment (Christenson et al 1991). The full therapeutic effect of fluoxetine may be delayed five weeks (PDR 1999). Furthermore, the long elimination half-lives of fluoxetine and its active metabolite, norfluoxetine, assume that, even when dosing is terminated, active drug substance will persist in the body for weeks, primarily depending on individual patient characteristics, previous dosing regimen and length of previous therapy at discontinuation (PDR 1999). Fifteen participants, fourteen female and one male, completed the study (Christenson et al 1991). No significant drug by period interactions were presented in weekly participant ratings of hair pulling, weekly participant ratings of the compulsion to pull hair, weekly assessments of the number of hair-pulling episodes, or the estimated amount of hair pulled per week (Christenson et al 1991). The authors concluded that the short-term efficacy of fluoxetine in the treatment of trichotillomania was not shown by this study.

Most studies, like the one above, examine the efficacy of a drug in the short term. Streichenwein and Thornby (1995) conducted a double-blind, placebo controlled study of fluoxetine in the treatment of trichotillomania over a longer period of time than a typical study. The authors studied sixteen patients over a thirty-one week trial to determine the efficacy of high doses of fluoxetine to treat trichotillomania. Results of past controlled trials of selective serotonin reuptake inhibitors in the treatment of trichotillomania have been mixed (Streichenwein & Thornby 1995). Open trials have suggested the efficacy of fluoxetine, but an eighteen-week double-blind, crossover study of fluoxetine in high doses found no significant difference from the placebo group (Streichenwein & Thornby 1995). The two studies discussed above illustrate these findings. The authors considered that the shorter duration of the treatment, the dose level, and the symptom monitoring might have affected the outcome. Streichenwein and Thornby (1995) wanted their study to address both dose level and treatment duration. The hypothesis was that fluoxetine would be superior to the placebo in the treatment of trichotillomania (Streichenwein & Thornby 1995). Participants in the fluoxetine condition received doses of up to eighty mg per day (Streichenwein & Thornby 1995). The thirty-one week trial began with an initial two-week placebo washout phase, followed by a twelve-week treatment period with either fluoxetine or placebo, as randomly assigned in a double-blind fashion (Streichenwein & Thornby 1995). Participants then all entered a five-week washout phase and then a crossover to the other treatment condition (Streichenwein & Thornby 1995). Sixteen patients, fourteen women and two men, from an original group of twenty-three, completed the study (Streichenwein & Thornby 1995). There were no significant differences between fluoxetine and placebo treatments for the measures of weekly severity of hair pulling, weekly severity of urge to pull, daily hair counts, or estimated hair pulled, or days of hair pulling (Streichenwein & Thornby 1995).

Despite the failures of placebo controlled, double-blind studies to demonstrate the efficacy of fluoxetine in the treatment of trichotillomania, other studies have found some success with other drugs. In a study that falls between a case study and an experiment, O'Sullivan et al (1998) reviewed ten cases of patients who had received venlafaxine treatment for trichotillomania. Venlafaxine is an antidepressant whose mechanism of action is believed to be associated with its potentiation of neurotransmitter action in the central nervous system (PDR 1999). Venlafaxine and its active metabolite, odesmethylvenlfaxine, are potent inhibitors of neuronal serotonin and norepinephrine and weak inhibitors of dopamine (PDR 1999). The patients in this study were among the patients who were being treated at the authors' clinic. These patients chose venlafaxine from all the different treatment options, both behavioral and pharmacologic approaches, presented to them (O'Sullivan et al 1998). The initial treatment with venlafaxine typically begins with seventy-five mg per day, administrated in two to three divided doses (PDR 1999). In outpatient settings, there is no evidence of usefulness of doses greater than 225 mg per day, however more severely depressed inpatients responded to a mean dose of 350 mg per day (PDR 1999). Certain patients, including more severely depressed patients may therefore respond more to higher doses, up to a maximum of 375 mg per day, generally in three divided doses (PDR 1999). In these cases, venlafaxine was given at a mean dose of 274 mg per day, with a range of 37.5 to 450 mg per day (O'Sullivan et al 1998). The mean treatment duration was 15.1 weeks, with a range of 8 to 28 weeks (O'Sullivan et al 1998). The retrospective review of these ten cases indicates that short-term treatment with venlafaxine improved the symptoms of trichotillomania; however the authors acknowledge the need for controlled trials. Indeed, because this study was a glorified case study, the same methodological problems plaguing case studies apply. As a result, no causality can be concluded. However, because the study looked at ten cases, there is more applicability to the general population.

In another study, which found some success in treatment, Christenson et al (1998) investigated fluvoxamine in an eight-week open-label study. This study also looked to test the hypothesis that the presence of compulsive hair pulling is predictive of selective serotonin reuptake inhibitor response. Fluvoxamine is a selective serotonin reuptake inhibitor chemically unrelated to other selective serotonin reuptake inhibitors and is indicated for treatment of obsessive compulsive disorder (PDR 1999). Its mechanism of action in obsessive compulsive disorder is presumed to be linked to its specific serotonin reuptake inhibition in brain neurons (PDR 1999). The dosing of fluvoxamine starts with an initial dose of fifty mg per day; and the maximum dose should not exceed 300 mg per day (PDR 1999). In this study, subjects underwent a two-week, drug-free baseline period, followed by treatment with fluvoxamine for eight weeks (Christenson et al 1998). Dosage was initiated at fifty mg per day and increased as tolerated to a total dose of 300 mg per day (Christenson et al 1998). For the fourteen subjects who completed the study and the five who dropped it, analysis revealed statistically significant improvements in several measures of hair pulling severity, including hair pulling episodes, but not in estimated hair pulled (Christenson et al 1998). Furthermore, the percentage of patients' compulsive hair pulling symptoms was predictive of treatment response (Christenson et al 1998). However, three subjects who chose to enter long-term treatment moved substantially back towards baseline by the end of six months (Christenson et al 1998). The authors conclude that fluvoxamine can moderately reduce symptoms during the short-term treatment of trichotillomania; however such responses may be short-lived in the event of extended treatment. Furthermore, the presence of compulsive hair pulling may be predictive of treatment response (Christenson et al 1998). The results of this study must be looked at in light of the fact that it was not a placebo controlled experiment; causality therefore cannot necessarily be inferred. In one of the studies above the researchers examined the long term benefits of drug treatment over a period of thirty-one weeks. Indeed, for a single study, thirty-one weeks is longer than most. As a researcher extends the time commitment required by a study, participant compliance falls off. However, in one follow-up study, investigators have been able to assess long-term drug treatment benefits for trichotillomania. The original study found clomipramine more effective than desipramine in treating trichotillomania (Swedo et al 1989). Swedo et al (1989) studied thirteen women with severe trichotillomania in a ten-week double-blind, crossover trial of clomipramine and desipramine. Clomipramine is an anti-obsessional drug that belongs to the class of pharmacologic agents known as tricyclic antidepressants; it is indicated in the treatment of obsessive compulsive disorder (PDR 1999). Clomipramine is presumed to influence obsessive and compulsive behaviors through its effects on serotonergic neuronal transmission; the actual neuro-chemical mechanism is unknown, but its capacity to inhibit the reuptake of serotonin is thought to be important (PDR 1999). Desipramine is an antidepressant of the tricyclic type whose precise mechanism of action is unknown; theory suggests that tricyclics restore normal levels of neurotransmitters by blocking the reuptake of these substances from the synapses in the central nervous system (PDR 1999). Evidence further suggests that secondary amine tricyclic antidepressants, including desipramine, have greater activity in blocking reuptake of norepinephrine (PDR 1999). Desipramine was chosen for comparison with clomipramine due to its equivalent antidepressant efficacy, its lack of anti-obsessional activity and the similarity of the drugs' side effects (Swedo et al 1989). In the study, a baseline evaluation was followed by a two-week, single-blind, placebo phase (Swedo et al 1989). The placebo phase was followed by the active-treatment trial (Swedo et al 1989). The active-treatment trial consisted of two consecutive five-week periods of treatment with either clomipramine or desipramine, administered in a double-blind manner with a randomly assigned order (Swedo et al 1989). The severity of the symptoms was reduced more by clomipramine than by desipramine (Swedo et al 1989). The participants reported that the compulsion decreased in intensity and that they were more able to resist the urge to pull out their hair during the treatment with clomipramine (Swedo et al 1989). The authors conclude that clomipramine appears to be effective in the short-term treatment trichotillomania.

A follow-up to the original study indicates that clomipramine may be effective in the long-term treatment of trichotillomania. Swedo et al (1993) report that in the initial study comparing clomipramine to desipramine in the treatment of trichotillomania three of the thirteen participants in the initial double-blind crossover trial had complete remissions during the five weeks of clomipramine treatment, and nine had at least a fifty percent reduction in the severity of symptoms. These results were maintained for six months (Swedo et al 1993). According to the authors, the chronicity of the disorder and reports of relapses after prolonged drug treatment begged the question of long-term outcome. Follow-up information was obtained, by in-person interviews at two to three years and telephones updates at 4.3±0.6 years, from the first sixteen women with trichotillomania who were first treated in the authors' clinic, including the thirteen reported on in 1989. For the group overall there was a 40%, moderate, reduction in the severity of symptoms at a mean of 4.3 years of follow-up (Swedo et al 1993). These results suggest that pharmacotherapy with selective serotonin-reuptake inhibitors may be of long-term benefit to some patients with trichotillomania.

Given the failure of any one drug treatment to prove consistently successful in placebo controlled, double-blind experiments, the current situation for anyone with trichotillomania looking for pharmaceutical treatment is not promising. However, the future is not without hope. Given the successes reported in case studies, the follow-up study on clomipramine, and in some of the open-label studies, further research on those leads may prove successful. As with any mental disorder, it is unlikely that a drug will be found in the foreseeable future that is completely successful all the time. However, it is conceivable that the medical community may yet discover a drug that is mostly successful most of the time. Much more research is needed. Indeed, revolutionary research is currently being undertaken. The Heffter Research Institute is currently funding research at the University of Arizona Medical School to examine the benefits patients with obsessive compulsive disorder derive from hallucinogen-assisted therapy (heffter.org/2000). The rationale behind this sort of therapy is based on reported case studies in which hallucinogens, such as LSD and psilocybin, have helped patients with obsessive compulsive disorder and related disorders, such as body dysmorphic disorder (heffter.org/2000). In one case, a man with obsessive compulsive disorder reported experiencing neither obsessions nor compulsions while under the influence of drugs; furthermore, after regular use of hallucinogens, the obsessions and compulsions went into remission for several months after ceasing drug use (heffter.org/2000). If studies on treating obsessive compulsive disorder with hallucinogen-assisted therapy prove successful, the research may be expanded to include trichotillomania, as other drug treatments for obsessive compulsive disorder have been in the past. For the present, taking into account the available choices for pharmaceutical treatment, a patient with trichotillomania should be prepared to try various medications in the hopes of finding one, or a combination thereof, that provides some relief until more research is done.

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