Posted by temoigneur on June 11, 2007, at 3:18:57
In reply to Modafinil (Provigil, Alertec) a short term miracle, posted by AdamCanada on June 11, 2007, at 0:26:22
Hey Adam... how are you... us Canucks have to stick together.. I suffered with unipolar atypical depression, (apathy no motivition/energy) with psychotic features... the psychosis included OCD like anxiety... social phobia... I've been on psychiatric drugs from every family that I know of, since age 16, (28 now) - I even took part in a study using an abortion pill for psychotic depression. Nothing let me carry on with life like I hoped I'd be able to.
For myself, like you... modafinil and stimulants like ritalin, dexedrine would work brilliantly for a few days... too well, I became *almost manic - high, laser like concentration on rit. and dex, felt wonderful and stilll had reasonable judgement. Then on the third day or so I would start to crash and spiral downward into paranoia delusions of guilt, horrible anxiety/OCD. For three years I gave up on finding anything that would allow me to live a normal life, and just vegetated on clomipramine and zyprexa, always coming off and landing myself in the hospital because I hated feeling like a lifeless zombie.
I tell you all this because there was a happy ending for me. I managed to get Abilify from the states, (you can get it through the special access program up here)... and after 4 months at the highest dose - 30mg, I'm now able to concomitantly take meds I was intolerant to before - I feel like a new person. Before Abilify I was either 'stoned' on heavy antipsychotics, drunk on clonazepam, (with caused severe memory impairment, mild depression, sedation, and major tolerance)... or europhoric on a stimulant like ritalin for a few days where I would try to cram in all the studying I could for the one course I was trying to hang on to.. before crashing into a dark anxiety and psychosis....
... Now on 30 mg abilify*** (see article) I can take dexedrine and caffeine without feeling euphoric and crashing... I just feel energized, and vibrant, for the most part. I'm hoping to replace caffeine with modafinil and finish my undergrad... and who knows.Abilify is thought to be unlike other antipsychotics in that for many it doesn't cause weight gain, and for some it is thought to regulate dopamine levels, rather than blocking them like zyprexa, risperidone... and turing you into a zombie. For me it's been profoundly effective agent... largely free of side effects. On it, I can take dexedrine, prozac, caffeine, wellbutrin and just feel energized and alert.... it's partial blocking activity at dopamine receptors has allowed me to feel the positive effects that some non psychotic ADHD responders get... I do feel good and look forward to each day. I'm not an expert, but I've tried nearly every drug available and I would be happy to give you suggestions based on how they worked for me, and any patterns any of us see from your descriptions...
Abilify 30mg
Wellbutrin 100mg
Prozac 30mg
Dexedrine 20mg
Clonazepam 1.75mg
Caffeine (lots) Hope to switch to modafinil - (described in following article as caffeine like substance with no tolerance)
St. John's wort 300-600mg** )don't add this without talking to a specialist possible seratonin sydrome with SSRI - maybe othersThe next article is from a renound psychiatric encylopaedia, (Kapplan and Saddock), on Abilify;
Aripiprazole (Abilify) ***
Aripiprazole is the most atypical of the atypical antipsychotic drugs. Whereas other classic and atypical antipsychotics block DA receptors, which is thought to account for their antipsychotic effects, aripiprazole is a partial agonist at DA type 1 (D1), DA type 2 (D2), DA type 3 (D3), and 5-HT type 1A (5-HT1A) receptors, as well as being a full 5-HT type 2A (5-HT2A) receptor antagonist. The partial agonist activity at DA receptors provides for a relative balance mechanism wherein approximately 20 percent of the action of a full agonist is achieved by aripiprazole. At the same time, in the face of high levels of endogenous DA release, the drug acts as a relative antagonist because of its receptor occupancy. This lack of full DA receptor blockade (i.e., only 80-percent complete) accounts for the drug's good side effect profile and the lack of increases in serum prolactin, and prolactin levels actually decrease on the drug because of its weak agonist properties.
Accordingly, most side effects are not dose related, and a single dose of 15 to 20 mg per day appears sufficient for treatment of schizophrenic and manic psychoses. The drug causes few EPSs, even at high doses, and is weight neutral. However, bipolar patients may be particularly sensitive to akathisia on drug initiation, and lower starting doses are therefore recommended. Very young children should be started and treated at 2.5 to 5.0 mg per day. One trial in acute mania was positive, and, in another trial, it was better tolerated than haloperidol and more effective at week 12. It is hoped that the combination of weak DA agonist effects, the partial agonist effects at the 5-HT1A receptor, and the antagonist effects on the 5-HT type 2 (5-HT2) receptor will equate to a good antidepressant profile.
The second last article, (longer) from the 'Journal of Affective Disorders' is on modafinil... the way it works isn't completely understood, but it's described as being similar to caffeine, without leading to tolerance. (I know this wasn't your experience:( and in a very few cases psychosis has been reported...Journal of Affective Disorders. Vol. 95(1-3)(pp 111-114), 2006.
Absence of mood switch with and tolerance to modafinil:
A replication study from a large private practice
by
Nasr S, Wendt B, Steiner K.
Nasr Psychiatric Services,
United States.
J Affect Disord. 2006 May 29;
Modafinil…Background: Fatigue is a common symptom of depression, especially the bipolar type. Modafinil is a wake-promoting agent that can alleviate fatigue in depressed patients. Many stimulants used to treat fatigue carry the risk of a switch into mania or hypomania in bipolar patients as well as the risk for tolerance or abuse. Method: A retrospective chart review was performed on all patients currently being seen in a large outpatient practice who received modafinil at some point during their treatment. Data collected included patient demographics, MiniSCID diagnoses, clinical diagnoses including history of substance abuse, and length and dosage of treatment with modafinil. Results: Of the 191 patients who were given modafinil at some point during their treatment, 105 patients remained on it for 2 months or more and 37% of these patients were bipolar (18 BPI and 21 BPII). In addition, 86 patients were on modafinil for less than 2 months and 31% of these patients were bipolar(16% BPI and 15% BPII). No patients in any group demonstrated a switch into mania or hypomania while on modafinil. There was also no significant difference in final modafinil dosage between patients who had a positive history of chemical abuse/dependence (290 mg/day) and those who did not (258 mg/day). Limitations: Retrospective chart review. Conclusions: Adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or developing tolerance or abuse of this medication. copyright 2006 Elsevier B.V. All rights reserved.
Absence of mood switch with and tolerance to modafinil: A replication study from a large private practice
Suhayl Nasr , a, , Burdette Wendta and Kathryn Steinera
aNasr Psychiatric Services, United States
Received 10 August 2005; revised 28 December 2005; accepted 6 January 2006. Available online 5 June 2006.
Abstract
Background
Fatigue is a common symptom of depression, especially the bipolar type. Modafinil is a wake-promoting agent that can alleviate fatigue in depressed patients. Many stimulants used to treat fatigue carry the risk of a switch into mania or hypomania in bipolar patients as well as the risk for tolerance or abuse.
Method
A retrospective chart review was performed on all patients currently being seen in a large outpatient practice who received modafinil at some point during their treatment. Data collected included patient demographics, MiniSCID diagnoses, clinical diagnoses including history of substance abuse, and length and dosage of treatment with modafinil.
Results
Of the 191 patients who were given modafinil at some point during their treatment, 105 patients remained on it for 2 months or more and 37% of these patients were bipolar (18 BPI and 21 BPII). In addition, 86 patients were on modafinil for less than 2 months and 31% of these patients were bipolar(16% BPI and 15% BPII). No patients in any group demonstrated a switch into mania or hypomania while on modafinil. There was also no significant difference in final modafinil dosage between patients who had a positive history of chemical abuse/dependence (290 mg/day) and those who did not (258 mg/day).
Limitations
Retrospective chart review.
Conclusions
Adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or developing tolerance or abuse of this medication.
Keywords: Modafinil; Tolerance; Switching
Article Outline
1. Introduction
2. Method
3. Results
4. Discussion
5. Conclusions
References1. Introduction
Bipolar patients experience depression more often than mania (Judd et al., 2003). Fatigue has been reported as a possible clue for bipolarity when patients present with depression (Mitchell et al., 2001). Many stimulants or activating antidepressants used to address fatigue and depressed mood carry the risk of a switch into mania or hypomania in bipolar patients (Boerlin et al., 1998, Goldberg and Truman, 2003 and Ghaemi et al., 2004).
Modafinil is a wake-promoting agent that is used to treat many conditions associated with fatigue, including depression (DeBattista et al., 2001 and Nasr, 2004). Modafinil's mechanism of action is possibly mediated through the histamine receptors in the anterior hypothalamus without affecting the dopamine pathways associated with dependence and reward usually targeted by the stimulants (Lin et al., 1996). Modafinil, therefore, may be associated with a lower risk of mood switching in depressed patients.
Substance abuse is an additional contributing factor to mood switching. It is frequently comorbid with affective disorders raising additional concern for abuse of stimulants by bipolar patients. Modafinil is a class IV drug with the potential for risk of tolerance or abuse. However in previous studies of modafinil for depression augmentation, there were no reports of modafinil-induced mania in participants except for 4 single case reports of modafinil-induced recurrence of psychosis (Menza et al., 2000, DeBattista et al., 2001, Carlson et al., 2004, Nasr, 2004, Fava et al., 2005 and Vorspan et al., 2005). There is also lack of evidence for its abuse potential even among cocaine dependent individuals (Warot et al., 1993).
The following study examines modafinil's effect on mood switching, dose stability, and abuse liability in a large series of affective disorder outpatients.
2. Method
A retrospective chart review was performed on all patients currently being seen in a private, rural, outpatient psychiatric office who received modafinil at some point during their treatment, usually as an adjunct to other medications. Data collected included patient demographics, MiniSCID diagnoses, clinical diagnoses including history of substance abuse, length and dosage of modafinil treatment, and concomitant use of mood stabilizers. Patients were monitored for manic or hypomanic symptoms (euphoria, dysphoria or irritability with increased activity and insomnia) during their regularly scheduled office appointments, and all changes in modafinil dosage were recorded to monitor for the development of tolerance to the medication. Abuse of modafinil was monitored through a log of prescribed amounts compared to office visit interval.
Because many patients did not take modafinil beyond 2 months, and because mood switching could have occurred in the beginning of treatment the total sample was divided into more or less than 2 months use. St Anthony Memorial Health Center's Institutional Review Board gave permission to conduct a nonidentifying review of records.
3. Results
Of approximately 1500 patient charts reviewed, 191 patients were given modafinil at some point during their treatment. There were 134 female patients, and 57 male patients. Over 95% of patients were Caucasian. The average age of all patients given modafinil was 49.3 (± 12.5, range: 20–82); 48.6 (± 13.4) for patients who quit within 2 months, and 49.8 (± 12.0) for patients who remained on at least 2 months. 31 patients had a clinical diagnosis of Bipolar I, 33 patients had a clinical diagnosis of Bipolar II, and 118 patients had a clinical diagnosis of unipolar depression. The remaining 9 patients were diagnosed with other mood disorders.
105 patients remained on it for 2 months or longer (18 BP I, 21 BP II), 60 patients remained on for one year or longer (11 BP I, 16 BP II) and 45 patients remained on for 2 or more years (7 BPI, 9 BPII). 86 patients were on modafinil for less than 2 months and 29% of these patients were bipolar (13 bipolar I, 12 bipolar II). The reasons for stopping the medicine within the first two months were for lack of efficacy (N = 34), cost (N = 32), or adverse events, mostly sleep related (N = 20). Patients who remained on modafinil for more than 2 months stayed on modafinil for an average of 21.9 months (± 16). The longest observation was for 55 continuous months of modafinil use. There was no difference in the frequency of use of mood stabilizers between the patients who were on modafinil for less than 2 months (42%), more than 2 months (45%), more than one year (50%) or longer than 2 years (51%). As expected there were more bipolar patients on mood stabilizers (69% BPI, 59% BPII) than unipolar patients (33%).
No patients in any group demonstrated a switch into mania/hypomania while on modafinil. There was a statistically significant trend (p < 0.02) for bipolar patients to have lower final doses of modafinil (230 mg/day ± 88) than unipolar patients (287 mg ± 128). There was no significant difference in final modafinil dosage between patients who had a positive history of chemical abuse/dependence (290 mg/day ± 114) and those who did not (258 mg/day ± 123). Only 15% of the patients required a dosage adjustment in either direction in the first few months with no further changes past the first 10 months. No patients requested earlier refills than needed or reported an increase of dosage on their own beyond the first 1 month of dosage titration.
4. Discussion
The present findings indicated that modafinil did not induce manic/hypomanic switches or either tolerance or abuse in either unipolar or bipolar patients whether or not they had a positive history of chemical abuse/dependence.
Zis and Goodwin (1979) reported that cycle frequency increases with advancing age. This puts patients in this study at higher risk for mood switching yet 45 patients observed for 2 or more years did not show any mood cycling on modafinil (Zis and Goodwin, 1979).
Several studies looked at stimulants for depression augmentation. A study by Feighner et al. of 13 Major Depressive Disorder and Bipolar, MAOI or TCA-resistant patients found that patients receiving stimulants for depression augmentation improved by 2.9 points on their CGI scores. During the course of treatment, however, one patient experienced hypomania (Feighner et al., 1985). Fawcett et al. studied 32 Major Depressive Disorder and Bipolar patients who switched from TCA's to MAOI's augmented by a stimulant (either pemoline or dextroamphetamine). They found that 78% of patients responded (scored 1–2 on the CGI) to at least one combination of MAOI and stimulant after 6 months or more. However, 5 of these patients developed hypomania (Fawcett et al., 1991).
El-Mallakh studied methylphenidate for depression augmentation in 14 bipolar depressed patients. By week twelve of the study, participants showed improvement on the Hamilton Depression Rating Scale and Psychiatric Symptom Assessment Scale. Three patients dropped out of the study after experiencing side effects, including one with hypomania (El-Mallakh, 2000).
Soutullo et al. compared 80 adolescents hospitalized with bipolar disorder who received current/past stimulant or antidepressant treatment. They reported that previous stimulant treatment was associated with a worse hospitalization course in bipolar patients (Soutullo et al., 2002). There was no effect of duration of treatment with modafinil on the frequency of use of mood stabilizers. It is of note that a third of the bipolar patients did not switch moods despite the absence of mood stabilizers from their medication regimen. This further supports the absence of an inherent mood switching effect of modafinil in affective disorder patients.
Several studies reported the use of modafinil for augmentation in unipolar depression. None has reported an onset of manic or hypomanic symptoms during the observation period of up to 12 weeks (Menza et al., 2000, DeBattista et al., 2001, Doghramji et al., 2002 and Fava et al., 2005). Bransfield (2004) reported in a naturalistic review of 237 patients in his office practice that 2 patients developed overstimulation on modafinil. A longer study of two years by Carlson et al. (2004) of 8 bipolar patients treated with modafinil for depression augmentation also found no cases of modafinil-induced mania or hypomania. It is interesting to note that, similar to the present study, these 8 bipolar patients improved on a lower dosage of modafinil than the unipolar patients. The difference in dosage between the two groups in the current study is not of sufficient magnitude to have a clinical significance and to explain the absence of mood switch in bipolar patients.
Previous studies have compared modafinil to other stimulants. Warot et al. compared the subjective effects of modafinil, caffeine, and amphetamine in a placebo-controlled, double blind study of 16 participants with no history of drug abuse. Participant responses on the Addiction Research Center Inventory (ACI), Profile of Mood States, and Visual Analog Scales reported that modafinil's effects were similar to that of caffeine, but different from amphetamine (Warot et al., 1993). Jasinski (2000) studied the abuse potential of modafinil compared to methylphenidate in 24 male participants with a history of cocaine abuse. Ratings on the Amphetamine scale showed that modafinil had minimal amphetamine-like effects compared to methylphenidate, which was shown to have euphoric effects. Conversely, a similar study by Jasinski of 12 females with a history of polysubstance abuse found statistically significant differences between modafinil and placebo groups on the ACI amphetamine scale and the BMG scale. The studies cited above suggest that modafinil had minimal euphoric effects at best compared with other stimulants such as amphetamines and methylphenidate. In a study of 9 cocaine abusers, Rush et al. (2002) reported an absence of addictive behavior or willingness to pay for modafinil compared to cocaine. Myrick et al. (2004) reviewed the abuse liability of modafinil and concluded that it has very low abuse potential. In the present study, once patients achieved a stable dose of modafinil in the first 10 months they maintained the same dosage for the duration of treatment.
This study confirms previous results of generally well-tolerated use of modafinil in affective disorder patients with little abuse, tolerance or mood switch in either unipolar or bipolar patients. Compared to other studies, this study has the advantage of a large sample size of patients who were observed over a longer period of time with documentation of the effect of substance abuse history on the dosage stability and absence of either tolerance or abuse of modafinil.
5. Conclusions
Modafinil can play an important role in the treatment of treatment-resistant depression and bipolar depression. This study demonstrates that adult affective disorder patients, whether unipolar or bipolar, can use modafinil to relieve symptoms of depression, including fatigue and sleepiness, without risking a switch in their mood or risk developing tolerance of this medication.
One more .....Modafinil and psychosis, (very rare)
Is Psychosis Exacerbated by Modafinil?
Modafinil (Provigil; Cephalon Inc, West Chester, Pa) is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy. The stimulant drug methylphenidate, which promotes wakefulness, has been reported to be useful in treating severe and persistent sedation associated with clozapine treatment.1 However, controversy has surrounded the routine use of such stimulant drugs to treat clozapine-induced sedation because of the potential risk of exacerbating psychosis (due to the drugs' dopaminergic activity) and worsening movement disorders.2 We herewith report on the possible exacerbation of psychosis by modafinil in a clozapine-treated patient with schizophrenia.
Our patient was a 61-year-old African American woman with a history of undifferentiated schizophrenia and neurolepsy-induced akathisia, who was stable with a regimen of 100 mg of clozapine administered 3 times daily by mouth and 1 mg of lorazepam twice daily by mouth. She had a history of hypertension for which she was being treated with 10 mg of amlodipine 4 times daily by mouth. She complained of severe daytime sedation that persisted for 2 months after the initiation of the clozapine trial. To treat the intractable sedation, 200 mg of modafinil (4 times daily by mouth) was added to her preexisting medication regimen. During week 3 of modafinil treatment, she visited in an agitated state with extreme disorganization of speech, paranoid delusions, and auditory hallucinations necessitating inpatient psychiatric care. The serum clozapine level determined on admission (approximately 12-16 hours after last dose) was 646 ng/mL, confirming compliance. The patient stabilized within 2 weeks after the discontinuation of modafinil, while maintaining her previous medications (clozapine, lorazepam, and amlodipine) at the same dosages. The baseline and follow-up Positive and Negative Symptom Scale (PANSS), Epworth Sleepiness Scale (ESS), and Abnormal Involuntary Movement Scale (AIMS) scores are presented in Table 1.
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Patient Scores*Modafinil has an essentially unknown mechanism of action as a sleep inhibitor and perhaps a subtle behavioral activating agent; it seems not to be directly monoaminergic, unlike traditional stimulants. It has been hypothesized that modafinil might promote wakefulness indirectly by inhibiting the release of -aminobutyric acid (GABA) in the forebrain, perhaps through a serotonin-mediated process.3 The N-methyl-D-aspartate (NMDA) glutamate receptor hypofunction hypothesis of schizophrenia proposes that a hypofunctional NMDA receptor system causes loss of GABAergic inhibition, which in turn leads to a loss of inhibition over the excitatory pathways (cholinergic and glutamatergic) that convergently innervate vulnerable cerebrocortical neurons involved in psychotic symptom formation.4 It is plausible that modafinil, via its inhibition of GABA release, aggravated the already depressed level of GABAergic inhibition in our schizophrenic patient, leading to an acute exacerbation of psychosis. At least theoretically, it is possible that modafinil tipped the balance in favor of psychosis. The patient's psychosis may have been stabilized by clozapine through its potential to enhance the release of GABA via its 5-HT2 antagonism5; and lorazepam, by its enhancement of activity at the GABA receptors.6 One must keep in mind that the fundamental underpinnings behind this hypothesis are speculative and that these findings need to be replicated at the clinical and basic science levels before researchers can draw any firm conclusions. Nevertheless, this case report suggests that this new, centrally acting agent modafinil may not be any safer than stimulants in patients with schizophrenia. It also suggests the need for further research into the basic pharmacological mechanism of modafinil and its utility as a possible indirect probe to study the NMDA receptor hypofunction hypothesis in schizophrenia.
Rajesh Narendran, MD, BS; Carolyn M. Young, MD; Antoinette M. Valenti,"
poster:temoigneur
thread:762296
URL: http://www.dr-bob.org/babble/20070604/msgs/762303.html