Хлорфенамин как антидепрессант

Chlorpheniramine, selective serotonin-reuptake inhibitors (SSRIs) and over-the-counter (OTC) treatment

Антидепрессанты сравнение рецепторных свойств

Compound	SERT	NET	DAT	H1	M1-5	α1	α2	5-HT1A	5-HT2	D2
Agomelatine	?	?	?	?	?	?	?	?	270	?
Amitriptyline	4.3	35	3250	0.95	9.6	24	690	450	18	1460
Amoxapine	58	16	4310	25	1000	50	2600	?	?	?
Atomoxetine	8.9	2.03	1080	5500	2060	3800	8800	10900	940	35000+
Bupropion	45026	1389	2784	11800	35000+	4200	35000+	35000+	35000+	35000+
Buspirone	?	?	?	?	?	138	?	5.7	174	362
Butriptyline	1360	5100	3940	?	?	?	?	?	?	?
Citalopram	1.16	4070	28100	?	?	?	?	?	?	?
Clomipramine	0.28	38	2190	31	37	38	3200	?	?	?
Desipramine	17.6	0.83	3190	60	66	100	5500	6400	350	3500
Dosulepin	8.6	46	5310	?	?	?	?	?	?	?
Doxepin	68	29.5	12100	0.17	23	23.5	1270	276	27	360
Duloxetine	0.8	7.5	240	?	?	?	?	?	?	?
Etoperidone	890	20000	52000	3100	35000+	38	570	85	36	2300
Femoxetine	11	760	2050	4200	184	650	1970	2285	130	590
Fluoxetine	0.81	240	3600	5400	590	3800	13900	32400	280	12000
Fluvoxamine	0.81	240	3600	?	?	?	?	?	?	?
Imipramine	1.4	37	8500	37	46	32	3100	5800	150	620
Lofepramine	70	5.4	18000	360	67	100	2700	4600	200	2000
Maprotiline	5800	11.1	1000	2	570	90	9400	?	?	?
Mazindol	100	1.4	11	?	?	?	?	?	?	?
Mianserin	4000	71	9400	?	?	?	?	?	?	?
Milnacipran	123	200	10000+	?	?	?	?	?	?	?
Mirtazapine	1500+	1250~	1500+	1~	1000~	500~	100~	1500+	10~	1500+
Nefazodone	200	360	360	24000	11000	48	640	80	26	910
Nisoxetine	383	5.1	477	?	?	?	?	?	?	?
Nomifensine	1010	15.6	56	?	?	?	?	?	?	?
Nortriptyline	18	4.37	1140	6.3	37	55	2030	294	41	2570
Oxaprotiline	3900	4.9	4340	?	?	?	?	?	?	?
Paroxetine	0.13	40	490	22000	108	4600	17000	35000+	19000	32000
Protriptyline	19.6	1.41	2100	25	25	130	6600	?	?	?
Reboxetine	720	11	10000+	?	?	?	?	?	?	?
Sertraline	0.29	420	25	24000	630	380	4100	35000+	9900	10700
Trazodone	160	8500	7400	1100	35000+	42	320	96	25.0	35000+
Trimipramine	149	2450	3780	0.27	58	24	680	?	?	?
Venlafaxine	82	2480	7647	35000+	35000+	35000+	35000+	35000+	35000+	35000+
Viloxazine	17300	155	100000+	?	?	?	?	?	?	?
Zimelidine	152	9400	11700	?	?	?	?	?	?	?

SERT, NET, and DAT correspond to the abilities of the compounds to inhibit the reuptake of serotonin, norepinephrine, and dopamine, respectively. The other values correspond to their affinity for various receptors.

http://en.wikipedia.org/wiki/Antidepressant

Аспирин при шизофрении

"Aspirin given as [an adjunct treatment] to regular antipsychotic treatment reduces the symptoms of schizophrenia spectrum disorders. The reduction is more pronounced in those with the more altered immune function. Inflammation may constitute a potential new target for antipsychotic drug development."

Aspirin for Schizophrenia?

Зипрасидон (зелдокс, геодон)

Focus on Ziprasidone

Потенциирование трийодтиронином при недостаточном ответе на терапию ТЦА

"The exact mechanism of action of T3 augmentation remains largely unknown. In depressed patients, the circulating plasma levels of free T4 appear to be normal,
but levels of free T3 may be decreased. Approximately one third of depressed patients show blunting of the TSH response to thyrotropin releasing hormone.
Approximately 15% of depressed patients have elevated basal TSH levels, probably indicating subclinical hypothyroidism, and thyroid autoantibodies
are found in a similar percentage of patients.11
Thyroid abnormalities are found at a higher frequency among TCA nonresponders and this may link with the underlying mechanism of T3 augmentation.In most case reports, patients had normal thyroid function, as in our second case. There seems to be no
relationship between thyroid state and the efficacy of T3 augmentation. In the first case, the patient had sick euthyroid syndrome, which is sometimes seen in
depressed patients. In this condition, peripheral deiodination of T4 to T3 is reduced, although the TSH level is normal.
One proposed mechanism of T3 augmentation is that T3 may raise peripheral thyroid hormone concentrations in patients with covert or borderline hypothyroidism. Other authorities believe that there is no difference in the thyroid state of the
responders and nonresponders to T3 augmentation. 12 L-triiodothyronine may act in euthyroid patients through augmentation of the β-adrenergic system.13 Alternatively, T3 may also affect thyroid utilisation and local neuronal deiodination in the brain."

"The usual dose of T3 in augmentation therapy is 25 µg/d to 50 µg/d. A starting dose of 20 µg increasing to 40 µg was given to the patients in this study. Initial improvement in mood is usually apparent within several days. Goodwin et al reported that there was improvement in all aspects of the depressive syndrome within 1 to 3 days. For the two patients in this study,initial responses were noted after 3 and 7 days. An adequate trial of T3 augmentation should last for 7 to 14 days to reach its full effect. If T3 augmentation is effective, most studies recommend a maintenance
period of 2 months before gradually reducing the dose at the rate of 10 µg every 3 to 7 days."

Triiodothyronine augmentation for the treatment of depression in substance misusers unresponsive to tricyclic antidepressants.

Омега-3, омега-6 и витамин D в предупреждении возникновения психотических симптомов

"Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic-like symptoms."

Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population

Фармакотерапия социофобии

Pharmacotherapy for Social Anxiety Disorder: An Update

Анксиолитический эффект сока черноплодной рябины у крыс

"The main biologically active constituents of Aronia melanocarpa fruit juice (AMFJ) are polyphenolics, amongst them flavonoids, mainly anthocyanins. The aim of the present study was to investigate the effects of AMFJ (5 and 10 mL/kg) on anxiety using the social interaction test, on locomotor activity in the open field test and on working memory in the object recognition test in rats. AMFJ showed an anxiolytic-like effect which was demonstrated by a dose-dependent increase in the time of active social contacts between the test partners. The effects of both AMFJ doses were comparable to the effect of diazepam (1 mg/kg). AMFJ neither changed significantly horizontal and vertical locomotor activity, nor did it adversely affect working memory. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved."

Anxiolytic-like effect of Aronia melanocarpa fruit juice in rats.

Прегабалин при ГТР

"These results indicate that pregabalin is an effective, rapidly acting, and safe treatment for generalized anxiety disorder. In short-term treatment, pregabalin does not appear to have the withdrawal symptoms associated with the benzodiazepines."

Pregabalin in Generalized Anxiety Disorder: A Placebo-Controlled Trial

"The dose of 150 mg pregabalin over the four weeks of the trials was found insufficient for the treatment of GAD. In the dose range of 200-450 mg daily, a clinically significant effect was obtained, although with a plateau-like curve which was not increased for the maximum dose of 600 mg daily."

Dose-response relationship of pregabalin in patients with generalized anxiety disorder. A pooled analysis of four placebo-controlled trials.

"The efficacy of pregabalin in treating GAD is not surprising as a number of other antiepileptic drugs have also been shown to have anxiolytic properties and to be effective in treating patients with anxiety disorders. Valproate has been shown to have efficacy in the treatment of panic disorder (Primeau et al 1990; Woodman and Noyes 1994; Baetz and Bowen 1998) and blocks lactate-induced panic attacks (Keck et al 1993). The antiepileptic drug carbamazepine has efficacy in the treatment of panic disorder (Tondo et al 1989), post-traumatic stress disorder (PTSD) (Lipper et al 1986), and obsessive compulsive disorder (OCD) (Joffe and Swinson 1987). Lamotrigine is potentially effective in the treatment of PTSD (Hertzberg et al 1999) and may have an adjunctive role in the treatment of refractive OCD (Kumar and Khanna 2000). Topiramate has been shown to be efficacious in open-label trials for PTSD (Berlant and van Kammen 2002; Berlant 2004), social phobia disorder (Van Ameringen et al 2004) and may have an adjunctive role in treatment-resistant OCD (Van Ameringen et al 2006). However, unlike previous antiepileptic drugs which primarily block sodium and potassium channels or increase cerebral GABA concentrations, pregabalin decreases presynaptic calcium currents and in doing so decreases the release of several neurotransmitters, including glutamate (Dooley et al 2000a), substance P (Fehenbacher et al 2003), calcitonin-gene-related peptide (Fehenbacher et al 2003), and norepinephrine (Dooley et al 2002). Interestingly, many of these neurotransmitters have been implicated in the pathogenesis GAD or other anxiety disorders (Erikkson et al 1991; Geracioti et al 2001; Olsson et al 2004; Geracioti et al 2006). As might be expected, agents that pharmacologically dampen these systems have therapeutic roles in a number of anxiety disorders (Peet and Ali 1986; Furmark et al 2005; Strawn and Geracioti 2006). Also, decreases in the activity of these or related “fear circuits” that underlie the pathophysiology of certain anxiety disorders (Stahl 2004) could explain the efficacy of pregabalin in patients with GAD. It will be of interest to examine the effects of pregabalin in other anxiety disorders such as PTSD, panic disorder, or even meal-related anxiety in anorexia nervosa (wherein additional benefit may be conferred by pregabalin-associated weight gain)."

The treatment of generalized anxiety disorder with pregabalin, an atypical anxiolytic

Антиконвульсанты в терапии поведенческих и психологических симптомов деменции

"INTRODUCTION: Dementia, besides the dominant cognitive disorders that define it, is associated with behavioral disturbances, the consequences of which are, on various levels, a determining factor for the handling of these patients. The treatment of behavioral and psychological symptoms is essential and although, to date, no therapeutic solution is satisfactory, it is necessary to look for an alternative to the neuroleptics usually employed, which raise real problems of tolerance in this geriatric population. BACKGROUND: For several years, anticonvulsants, among which some have shown mood stabilizing activity, have been the object of research in this indication. The purpose of this review of the literature is to assess the interest and the limits of anticonvulsant mood stabilizers (carbamazepine, valproic acid, gabapentin, lamotrigine, topiramate, oxcarbazepine) in the treatment of the so-called "noncognitive" symptoms of dementia. Their mechanism of action in mood disorders is not well known, but it would appear to be via the modulation of glutamate-mediated excitatory synaptic transmission and gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission that anticonvulsants might reduce behavioral symptoms in demented patients. METHODS: The method employed in this work was a systematic bibliographic review, in which only the double-blind placebo-controlled studies or the clinically detailed enough open-labelled studies using validated scales were retained. RESULTS: Among these medications, only carbamazepine demonstrated its efficacy in behavioral and psychological symptoms of dementia (BPSD) in controlled studies, notably that of Tariot et al. [J Am Geriatr Soc 42 (1994) 1160-1166 and Am J Psychiatry 155 (1998) 54-61] and Olin et al. [Am J Geriatr Psychiatry 9 (2001) 400-405], but with significant adverse events (sedation, hyponatremia, cardiac toxicity), particularly in the elderly and, being a strong enzymatic inducer, with a high likelihood of drug-drug interactions. Valproic acid showed some interesting results in BPSD within a large number of open studies and case reports. However, among the five controlled studies that have been published [Curr Ther Res 62 (2001) 51-67; Am J Geriatr Psychiatry 9 (2001) 58-66; Int J Geriatr Psychiatry 17 (2002) 579-585; Curr Alzheimer Res 2 (2005) 553-558 and Am J Geraitr Psychiatry 13 (2005) 942-945], none confirmed its efficacy on these symptoms. Regarding its tolerability in the geriatric population, no notable major side effect was reported (haematologic and hepatic effects are not more frequent than in the general population), except possible excessive sedation. Moreover, it appears that valproic acid could have neuroprotective effects, even if the contrary has been observed in a recent study. More studies need to be (and are being) conducted, notably on the interest of valproic acid in prophylaxis of BPSD. Gabapentin seems to be worthwhile and well tolerated in this indication, but no controlled study has been conducted to prove its efficacy, even if a quite important number of case reports and open studies have shown encouraging results. Concerning lamotrigine, which may potentially induce severe cutaneous side effects when administered with valproic acid, this drug has shown its efficacy in bipolar disorders and two recent case reports seem to indicate some interest in BPSD. Furthermore, lamotrigine appears to have neuroprotective effects. Although topiramate has shown interesting results in one open study in BPSD, its use in demented patients cannot be recommended because of its deleterious effect on cognitive functions. Oxcarbazepine, theoretically, could be an alternative to carbamazepine, which is, as aforesaid, the only anticonvulsant that proved its interest in BPSD. However, no clinical study has yet been published to support this hypothesis. This drug is better tolerated than carbamazepine, but induces severe and more frequent hyponatremia. DISCUSSION AND CONCLUSION: Finally, although we all know that antipsychotics should no longer be prescribed in the elderly, the treatment of behavioral and psychological symptoms of dementia remains a difficult problem, considering the lack of a real alternative to these medications. Anticonvulsant mood stabilizers are an interesting solution but none of them, other than carbamazepine, which did, but which is not better tolerated than the usual drugs in this population - was able to prove its efficacy in this indication. Among these medications, valproic acid, gabapentin and lamotrigine should be studied further, and the neuroprotective effect of some of them is an interesting route for research."

Anticonvulsant mood stabilizers in the treatment of behavioral and psychological symptoms of dementia (BPSD)

Влияние современных антиконвульсантов на когнитивные функции

"BACKGROUND: Antiepileptic drugs (AEDs) can be associated with neurotoxic side effects including cognitive dysfunction, a problem of considerable importance given the usual long-term course of treatment. Pregabalin is a relatively new AED widely used for the treatment of seizures and some types of chronic pain including fibromyalgia. We measured the cognitive effects of 12 weeks of pregabalin in healthy volunteers. METHODS: Thirty-two healthy volunteers were randomized in a double-blind parallel study to receive pregabalin or placebo (1:1). Pregabalin was titrated over 8 weeks to 600 mg/d. At baseline, and after 12 weeks of treatment, all subjects underwent cognitive testing. Test-retest changes in all cognitive and subjective measures were Z scored against test-retest regressions previously developed from 90 healthy volunteers. Z scores from the placebo and pregabalin groups were compared using Wilcoxon tests. RESULTS: Thirty subjects completed the study (94%). Three of 6 target cognitive measures (Digit Symbol, Stroop, Controlled Oral Word Association) revealed significant test-retest differences between the pregabalin and placebo groups, all showing negative effects with pregabalin (p < 0.05). These cognitive effects were paralleled by complaints on the Portland Neurotoxicity Scale, a subjective measure of neurotoxicity (p < 0.01). CONCLUSION: At conventional doses and titration, pregabalin induced mild negative cognitive effects and neurotoxicity complaints in healthy volunteers. These effects are one factor to be considered in the selection and monitoring of chronic AED therapy. Class of Evidence: This study provides Class I evidence that pregabalin 300 mg BID negatively impacts cognition on some tasks in healthy volunteers."

Cognitive effects of pregabalin in healthy volunteers: a double-blind, placebo-controlled trial.

"OBJECTIVE: To evaluate the cognitive effects of topiramate (TPM) and gabapentin (GBP). METHODS: Forty healthy volunteers were randomized to a 12-week course of TPM, GBP, or placebo. Doses were gradually escalated over 10 weeks to a maximum of 400 mg/day of TPM or 3,600 mg/day of GBP or to the highest tolerated dose. Subjects were interviewed and examined biweekly. Cognitive testing was performed prior to initiating the drug and again 12 weeks later, at least 2 weeks after achieving plateau dosing. For each subject and cognitive measure, test-retest Z scores were calculated based on regression equations derived from 73 healthy volunteers. Group comparisons utilized the Wilcoxon test. RESULTS: There were significant TPM vs GBP and TPM vs placebo differences in test-retest Z scores for four of six target cognitive measures (Digit Symbol, Story Recall, Selective Reminding, Controlled Oral Word Association), always indicating worse retest performance for subjects receiving TPM. Overall, 12 of 24 cognitive measures were similarly affected. TPM effects were large, and several target measures averaged >2 SD of negative change. One measure was significantly affected by GBP. CONCLUSIONS: Topiramate (TPM) impaired cognitive test performance, whereas gabapentin had minimal effects. The effects of TPM were of sufficient magnitude potentially to affect daily and occupational function."

Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers.

Кветиапин: эффективность и переносимость доз

"Quetiapine has a wide clinical dose range that extends up to 750mg/day (up to 800 mg/day in the USA and Canada).[21,22] Although administration is usually twice-daily,[23] a pilot study in patients with schizophrenia or schizoaffective disorder found similar levels of clinical efficacy in patients administered quetiapine on a once-or twice-daily basis.[24] Moreover, our clinical experience has suggested that a more rapid initiation schedule than that described in current prescribing information (300 mg/day by Day 4; 300-400 mg/day by Day 4 in the USA and Canada),[21] with a higher target dose, may be more appropriate in hospitalised adult and adolescent patients with an acute exacerbation of schizophrenia in order to achieve rapid control of symptoms. Some evidence supporting this assertion can be found in a poster that described a randomised, multicentre, double-blind, pilot study of hospitalised patients with acute schizophrenia who had their doses of quetiapine (twice-daily oral administration) titrated to 400 mg by Days 2, 3 or 5, without any increased risk of adverse events compared with classic initiation.[25] The overall frequency of adverse events was similar among the three initiation groups and somnolence was experienced by fewer than 15% of patients in each initiation group; indeed, the lowest incidence of somnolence (8%) was observed in the group of patients using the fastest initiation scheme (400 mg by Day 2). Throughout the study, patient vital signs and laboratory values were similar among the three initiation groups. The somnolence observed in these quetiapine-treated patients is likely to be a result of histamine H1 antagonism to which tolerance usually develops over time. Experience has shown that somnolence with quetiapine is not dose-related, most cases are mild and transient (usually dissipating after approximately 2 weeks), and that the incidence of somnolence does not increase over time. These data support our clinical experience of initiating quetiapine at 200mg/day in the inpatient setting and increasing the dose in increments of 200 mg/day."

Dosing of quetiapine and Clinical Global Improvement scores in a small study of patients with schizophrenia, schizoaffective disorder or other psychotic disorders.

Managing Acute Exacerbations of Schizophrenia: Focus on: Influence of Tolerability on Treatment Selection

Рецепторный профиль анитипсихотиков второго поколения и галоперидола

Receptor Binding Profile of Aripiprazole and Reference Antipsychotics^a

Receptor	Aripiprazole	Olanzapine	Risperidone	Quetiapine	Ziprasidone	Clozapine	Haloperidol
D1	265b	31	430	455	525	85	210
D2	0.34b	11	4	160	5	126	0.7
D3	0.8b	49	10	340	7	473	2
D4	44b	27	9	1600	32	35	3
5-HT1A	1.7b	>10,000	210	2800	3	875	1100
5-HT2A	3.4b	4	0.5	295	0.4	16	45
5-HT2C	15b	23	25	1500	1	16	>10,000
a1	57	19	0.7	7	11	7	6
H1	61b	7	15	11	50	6	440
M1	>10,000	1.9	>10,000	120	>1000	1.9	>150

Aripiprazole in the Treatment of Schizophrenia

Гэмблинг вызваный прамипексолом

BACKGROUND: Dopamine agonists (DAs), long used in treating Parkinson’s disease and effective in relieving symptoms of restless legs syndrome, have frequently been reported to induce problematic compulsive behaviors (e.g., obsessive gambling, hypersexuality) in individuals who had never had difficulties with such behaviors before. OBJECTIVE: The authors report two cases that add to a small-but-growing literature suggesting that these drugs be dispensed with appropriate caution. METHOD: The authors describe two patients seen in a psychiatric setting—one, after a suicide attempt, and one with depression—both resulting from intractable compulsive gambling. RESULTS: In both instances, control of gambling was achieved: in one, when pramipexole was discontinued, and in the other, after substitution of ropinirole and addition of spiritual and support-group approaches. DISCUSSION: DAs stimulate pathways that govern reward behavior, including pleasure and addiction. Other reward behaviors, such as eating and sexual activity, may also be affected by DAs. These cases demonstrate a clear temporal relationship between initiation and behavioral change; patients and their caregivers should be alerted to the possibility of such changes.

Impact of Dopamine Agonists on Compulsive Behaviors: A Case Series of Pramipexole-Induced Pathological Gambling

Психогенная пурпура

Case Report: Psychogenic Purpura