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Bluelighter
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- Aug 19, 2017
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Electroconvulsive therapy in the treatment of depression in a former ecstasy user.
Abstract
Depression in former ecstasy users may not respond to selective serotonin reuptake inhibitors (SSRIs) possibly due to damaged serotonergic synapses following long-term heavy ecstasy use. We report findings in a patient suffering from MDMA-induced depression which was refractory to several antidepressive medications including selective noradrenergic reuptake inhibitor (SNRI) and SSRI. An add-on repeated bilateral electroconvulsive therapy (EET) was able to achieve a stable remission of affective and cognitive symptoms with a follow-up of more than 1.5 years.
Add-on ECT could be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and/or SNRI. Clinical trials are needed to evaluate further the usefulness of ECT in this patient group.
Keywords
MDMA, ecstasy, depression, 5-HT, neurotoxicity, electroconvulsive therapy
Introduction
MDMA (3,4-methylenedioxymetamphetamine), the most prominent substance of the ecstasy group, is selectively neurotoxic to serotonergic axon terminals in animals (Ricaurte et al., 1988. In humans, some but not all studies indicated that long-term heavy ecstasy use can result in serotonergic dysfunction, e.g. reduced brain concentrations of 5-hydroxyindoleacetic acid (McCann et al., 1994) and reduced densities of the presynaptic serotonin reuptake transporters (SERT) (McCann et al., 1998; Thomasius et al., 2003). It is compelling to link these changes to the variety of psychiatric symptoms that many ecstasy users develop after chronic use, even if they became abstinent (Morgan, 2000; Kalant, 2001). The typical combination of symptoms is suggestive of serotoner-gic dysfunction, affecting emotion (depressed mood, anxiety; Morgan, 2000; Verheyden et al., 2003), cognition (disturbed verbal memory and executive functions; Gouzoulis-Mayfrank et al., 2003; Thomasius et al., 2003), behaviour (impulsivity; Morgan, 2000) and vegetative functions (disturbed sleep, sexuality, appetite; Morgan, 2000; Thomasius et al., 2003).
It has been proposed to treat depression in ecstasy users with selective serotonin reuptake inhibitors (SSRIs) (Kalant, 2001). However, it has also been recommended to use selective noradrenergic reuptake inhibitors (SNRI, e.g. reboxetine) in case of a lack of response to SSRI treatment, which may be due to a damaged serotonergic system in ecstasy users (Haddad et al., 2002). However, controlled studies are not available, yet. We present the case of a former heavy ecstasy user with major depressive disorder that was refractory to pharmacological treatment including SSRI and SNRI, but responded well to add-on electroconvulsive therapy (ECT).
Case report
Mr A was a 28-year-old man presenting with depressive symptoms (low mood, loss of interest, anhedonia, reduced energy) and cognitive disturbances (difficulties in reading, inability to concentrate). He also suffered from derealization, metamorphopsia of his nose and ears, strange body sensations, ideas of reference and thought echo (while reading messages on the mobile phone) without delusional character. He was a former heavy ecstasy user in the fifth year of abstinence who had never taken other illicit drugs. Before, he had been using ecstasy for 5 years, with doses increasing from a quarter of a tablet to up to ten pills per weekend. The estimated lifetime dose was 200 to 1000 ecstasy tablets. First symptoms already appeared while taking ecstasy. They increased gradually over the years despite stopping ecstasy use. A year ago, he first sought professional help for depressive symptoms. Citalopram 20 mg once daily was not effective. Medical as well as personal and family psychiatric histories were empty (except for Scheuermann's disease). Physical examination was unremarkable. Contrast enhanced cranial magnetic resonance imaging did not reveal any pathologies. EEG, ECG, laboratory tests (including thyroid parameters, rheumatologic/vasculitis screening, HIV, borrelia burgdorferi and treponema pallidum-antibodies) and cerebrospinal fluid was normal. Toxicology screening was negative. Neuropsychological testing showed impaired sustained and divided attention (as measured by sub-tests from a German test battery on attentional processes; Zimmermann and Fimm, 1994), verbal working memory (Digit Span) as well as deficits in planning and problem solving (Wisconsin Card Sorting Test). Psychopathological ratings yielded the following scores on admission: Clinical Global Impressions (CGI) 5, Hamilton Depression Rating Scale (HAMD-21) 32, Brief Psychiatric Rating Scale sum score (BPRS) 59.
A diagnosis of depressive disorder not otherwise specified (DSM-IV-TR 311) was made. The former long-term heavy ecstasy use was considered to be the main aetiological factor so that the diagnostic criteria for major depressive disorder were not met.
Several antidepressive medications failed, despite sufficient duration and plasma levels and rather aggravated the alterations of perception, e.g. citalopram (40 mg daily, plasma level 60 ng/ml, desmethyl-citalopram plasma level 34 ng/ml). Also, venlafaxine XR (225 mg daily) and the combination of bupropion (450 mg daily) and trimipramine (150 mg daily) were not effective, i.e. substances that do not rely on an intact serotonergic system and have a noradrenergic or dopaminergic mechanism of action. Moreover, the SNRI reboxetine was not tolerated by the patient (already 2 mg daily). Antipsychotic treatment with olanzapine (up to 25 mg daily, plasma level 60 ng/ml) or combinations of antidepressants and antipsychotics, e.g. citalopram/olanzapine, fluvoxamine/clozapine as well as venlafaxine XR/risperidone were not successful. Lithium as an augmentation strategy was not considered as there was no partial response on any of the antidepressants, and the clinical course imposed prompt amelioration.
The disorder was considered refractory to medication. Therefore, a series of eight sessions of electroconvulsive therapy was started after written informed consent had been obtained from the patient. The patient was still taking venlafaxin 225 mg and risperidone 2 mg daily. After five ineffective ECT sessions with unilateral stimulation over the right hemisphere three further sessions with bilateral stimulation were performed. Within days, a complete and stable remission of depressive, cognitive and psychotic symptoms was achieved. Rating scales (CGI 2, HAMD-21 8, BPRS 26) and a second neuropsychological testing confirmed improvement to normal. ECT treatment was well tolerated. The patient was discharged from hospital and went to work again. He remained in full remission for the next 1.5 years (follow-up).
Discussion and implications for clinical care
To our knowledge, this is the first report of successful ECT in a former heavy ecstasy user with depression refractory to medication. The symptoms failed to respond to SSRI (as can be expected from the concept of serotonergic neurotoxicity), but also antidepressive strategies bypassing the 5-HT system (such as reboxetine, venlafaxine, bupropion) were not helpful in treating the patient's symptoms.
It is of note however, that ECT was administered as an add-on to a medication that increases noradrenergic neurotransmission (venlafaxine plus risperidone). Despite the failure of reboxetine, this mechanism of action may have contributed to the overall effect; however, venlafaxine without ECT add-on was ineffective despite sufficient dosage and duration, suggesting a specific effect of ECT.
Concerning the possible neuronal mechanism of ECT, recent studies have shown that electroconvulsive seizures (ECS), the animal model for ECT, reduce beta-adrenergic receptors in the hippocampus and the frontal cortex (like some antidepressants), and result in an increase in brain-derived neurotropbic factor (BDNF) in the same brain areas (like MAO-inhibitors, but not SSRI and tricyclic antidepressants; Altar et el., 2003).
Although case studies require cautious interpretation, ECT might be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and, in particular, to noradrenergic antidepressants. Clinical trials are recommended to investigate further on the efficacy of add-on ECT or ECT in this patient group. At present, as for other forms of depression, ECT should be considered in MDMA-related depression whenever there was no response on several standard antidepressants and the clinical course is severe or necessitates prompt therapeutic success (see also, e.g. American Psychiatric Association, 2000).
Abstract
Depression in former ecstasy users may not respond to selective serotonin reuptake inhibitors (SSRIs) possibly due to damaged serotonergic synapses following long-term heavy ecstasy use. We report findings in a patient suffering from MDMA-induced depression which was refractory to several antidepressive medications including selective noradrenergic reuptake inhibitor (SNRI) and SSRI. An add-on repeated bilateral electroconvulsive therapy (EET) was able to achieve a stable remission of affective and cognitive symptoms with a follow-up of more than 1.5 years.
Add-on ECT could be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and/or SNRI. Clinical trials are needed to evaluate further the usefulness of ECT in this patient group.
Keywords
MDMA, ecstasy, depression, 5-HT, neurotoxicity, electroconvulsive therapy
Introduction
MDMA (3,4-methylenedioxymetamphetamine), the most prominent substance of the ecstasy group, is selectively neurotoxic to serotonergic axon terminals in animals (Ricaurte et al., 1988. In humans, some but not all studies indicated that long-term heavy ecstasy use can result in serotonergic dysfunction, e.g. reduced brain concentrations of 5-hydroxyindoleacetic acid (McCann et al., 1994) and reduced densities of the presynaptic serotonin reuptake transporters (SERT) (McCann et al., 1998; Thomasius et al., 2003). It is compelling to link these changes to the variety of psychiatric symptoms that many ecstasy users develop after chronic use, even if they became abstinent (Morgan, 2000; Kalant, 2001). The typical combination of symptoms is suggestive of serotoner-gic dysfunction, affecting emotion (depressed mood, anxiety; Morgan, 2000; Verheyden et al., 2003), cognition (disturbed verbal memory and executive functions; Gouzoulis-Mayfrank et al., 2003; Thomasius et al., 2003), behaviour (impulsivity; Morgan, 2000) and vegetative functions (disturbed sleep, sexuality, appetite; Morgan, 2000; Thomasius et al., 2003).
It has been proposed to treat depression in ecstasy users with selective serotonin reuptake inhibitors (SSRIs) (Kalant, 2001). However, it has also been recommended to use selective noradrenergic reuptake inhibitors (SNRI, e.g. reboxetine) in case of a lack of response to SSRI treatment, which may be due to a damaged serotonergic system in ecstasy users (Haddad et al., 2002). However, controlled studies are not available, yet. We present the case of a former heavy ecstasy user with major depressive disorder that was refractory to pharmacological treatment including SSRI and SNRI, but responded well to add-on electroconvulsive therapy (ECT).
Case report
Mr A was a 28-year-old man presenting with depressive symptoms (low mood, loss of interest, anhedonia, reduced energy) and cognitive disturbances (difficulties in reading, inability to concentrate). He also suffered from derealization, metamorphopsia of his nose and ears, strange body sensations, ideas of reference and thought echo (while reading messages on the mobile phone) without delusional character. He was a former heavy ecstasy user in the fifth year of abstinence who had never taken other illicit drugs. Before, he had been using ecstasy for 5 years, with doses increasing from a quarter of a tablet to up to ten pills per weekend. The estimated lifetime dose was 200 to 1000 ecstasy tablets. First symptoms already appeared while taking ecstasy. They increased gradually over the years despite stopping ecstasy use. A year ago, he first sought professional help for depressive symptoms. Citalopram 20 mg once daily was not effective. Medical as well as personal and family psychiatric histories were empty (except for Scheuermann's disease). Physical examination was unremarkable. Contrast enhanced cranial magnetic resonance imaging did not reveal any pathologies. EEG, ECG, laboratory tests (including thyroid parameters, rheumatologic/vasculitis screening, HIV, borrelia burgdorferi and treponema pallidum-antibodies) and cerebrospinal fluid was normal. Toxicology screening was negative. Neuropsychological testing showed impaired sustained and divided attention (as measured by sub-tests from a German test battery on attentional processes; Zimmermann and Fimm, 1994), verbal working memory (Digit Span) as well as deficits in planning and problem solving (Wisconsin Card Sorting Test). Psychopathological ratings yielded the following scores on admission: Clinical Global Impressions (CGI) 5, Hamilton Depression Rating Scale (HAMD-21) 32, Brief Psychiatric Rating Scale sum score (BPRS) 59.
A diagnosis of depressive disorder not otherwise specified (DSM-IV-TR 311) was made. The former long-term heavy ecstasy use was considered to be the main aetiological factor so that the diagnostic criteria for major depressive disorder were not met.
Several antidepressive medications failed, despite sufficient duration and plasma levels and rather aggravated the alterations of perception, e.g. citalopram (40 mg daily, plasma level 60 ng/ml, desmethyl-citalopram plasma level 34 ng/ml). Also, venlafaxine XR (225 mg daily) and the combination of bupropion (450 mg daily) and trimipramine (150 mg daily) were not effective, i.e. substances that do not rely on an intact serotonergic system and have a noradrenergic or dopaminergic mechanism of action. Moreover, the SNRI reboxetine was not tolerated by the patient (already 2 mg daily). Antipsychotic treatment with olanzapine (up to 25 mg daily, plasma level 60 ng/ml) or combinations of antidepressants and antipsychotics, e.g. citalopram/olanzapine, fluvoxamine/clozapine as well as venlafaxine XR/risperidone were not successful. Lithium as an augmentation strategy was not considered as there was no partial response on any of the antidepressants, and the clinical course imposed prompt amelioration.
The disorder was considered refractory to medication. Therefore, a series of eight sessions of electroconvulsive therapy was started after written informed consent had been obtained from the patient. The patient was still taking venlafaxin 225 mg and risperidone 2 mg daily. After five ineffective ECT sessions with unilateral stimulation over the right hemisphere three further sessions with bilateral stimulation were performed. Within days, a complete and stable remission of depressive, cognitive and psychotic symptoms was achieved. Rating scales (CGI 2, HAMD-21 8, BPRS 26) and a second neuropsychological testing confirmed improvement to normal. ECT treatment was well tolerated. The patient was discharged from hospital and went to work again. He remained in full remission for the next 1.5 years (follow-up).
Discussion and implications for clinical care
To our knowledge, this is the first report of successful ECT in a former heavy ecstasy user with depression refractory to medication. The symptoms failed to respond to SSRI (as can be expected from the concept of serotonergic neurotoxicity), but also antidepressive strategies bypassing the 5-HT system (such as reboxetine, venlafaxine, bupropion) were not helpful in treating the patient's symptoms.
It is of note however, that ECT was administered as an add-on to a medication that increases noradrenergic neurotransmission (venlafaxine plus risperidone). Despite the failure of reboxetine, this mechanism of action may have contributed to the overall effect; however, venlafaxine without ECT add-on was ineffective despite sufficient dosage and duration, suggesting a specific effect of ECT.
Concerning the possible neuronal mechanism of ECT, recent studies have shown that electroconvulsive seizures (ECS), the animal model for ECT, reduce beta-adrenergic receptors in the hippocampus and the frontal cortex (like some antidepressants), and result in an increase in brain-derived neurotropbic factor (BDNF) in the same brain areas (like MAO-inhibitors, but not SSRI and tricyclic antidepressants; Altar et el., 2003).
Although case studies require cautious interpretation, ECT might be a treatment option in former ecstasy users with severe depressive disorders that fail to respond to SSRI and, in particular, to noradrenergic antidepressants. Clinical trials are recommended to investigate further on the efficacy of add-on ECT or ECT in this patient group. At present, as for other forms of depression, ECT should be considered in MDMA-related depression whenever there was no response on several standard antidepressants and the clinical course is severe or necessitates prompt therapeutic success (see also, e.g. American Psychiatric Association, 2000).
I used ecstasy weekly for 6 years, history of mental illness since childhood and so far I have heard mixed reviews on ECT. Am willing to try it if all options are exhausted.
