In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight; about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight; about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight; about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight; about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight; about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and the film coating may be, e.g., about 1-10%, about 4-6%, or about 3.5% of the weight of the dosage form or tablet.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; and about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.01-1%, about 0.03-0.5%, or about 0.1% silicone dioxide colloidal by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; and about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 50-80%, about 60-70%, about 63-66%, or about 64.6% microcrystalline cellulose by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight.

In some embodiments, the dosage form contains reboxetine free base, such as about 4-6 mg, about 4.5-5.5 mg, or about 5 mg of reboxetine free base, or a molar equivalent amount of a salt form of reboxetine, such as about 5.5-7.5 mg, about 6-7 mg, or about 6.5 mg of reboxetine mesylate; about 10-30%, about 15-25%, about 20-22%, or about 21.5% of calcium phosphate dibasic dihydrate by weight; about 2.5-10%, about 4-7.5%, or about 5% hydroxypropyl methylcellulose by weight; about 1-10%, about 2-5%, or about 2.5% polyvinylpolypyrrolidone by weight; and about 0.1-5%, about 0.3-2.5%, or about 0.5% magnesium stearate by weight.

In some embodiments, the composition comprises about 2% to about 4% reboxetine by weight, or about 2-4%, about 2-2.5%, about 2.5-3%, about 3-3.5%, about 3.5-4%, about 2-3%, about 3-4% reboxetine free base by weight, or a molar equivalent amount of a salt form of reboxetine.

Additional examples of suitable dosage form compositions are listed in Table 1 below.

TABLE 1

Ingredient
% w/w

INTRA-GRANULAR

Reboxetine
3-4

Diluent
75-95

Binder
2.5-7.5

Disintegrant
1-5

Total Intra-Granular Composition
90-99

EXTRA-GRANULAR

Glidant
0.01-1

Disintegrant
1-5

Lubricant
0.1-1

Total Extra-Granular Composition
1-10

FILM COAT

Blend of polymer, plasticizer, and pigment
2-5

TABLE 2

Ingredient
% w/w

INTRA-GRANULAR

Reboxetine
3-4

Diluent 1
60-70

Diluent 2
15-25

Binder
2.5-7.5

Disintegrant
1-5

Total Intra-Granular Composition
90-99

EXTRA-GRANULAR

Glidant
0.01-1

Disintegrant
1-5

Lubricant
0.1-1

Total Extra-Granular Composition
1-10

FILM COAT

Blend of polymer, plasticizer, and pigment
2-5

TABLE 3

Ingredient
Function
% w/w

INTRA-GRANULAR

Reboxetine Mesylate
Active
3-4

Microcrystalline Cellulose
Diluent
60-70

Calcium Phosphate Dibasic Dihydrate
Diluent
15-25

Hydroxypropyl methylcellulose
Binder
2.5-7.5

Polyvinylpolypyrrolidone
Disintegrant
1-5

Total Intra-Granular Composition

90-99

EXTRA-GRANULAR

Silicone Dioxide Colloidal
Glidant
0.01-1

Polyvinylpolypyrrolidone
Disintegrant
1-5

Magnesium Stearate
Lubricant
0.1-1

Total Extra-Granular Composition

1-10

FILM COAT

Blend of polymer, plasticizer, and pigment
Film coating
2-5

Some dosage forms may comprise a uniform blend of reboxetine and a pharmaceutically acceptable excipient. In some embodiments, a pharmaceutical composition comprises a uniform blend of reboxetine and a pharmaceutically acceptable excipient. The excipient may be, for example, a diluent, a binder, a disintegrant, a glidant, a lubricant, or a combination thereof. In some embodiments, a pharmaceutical composition or a dosage form may comprise a uniform blend of reboxetine a diluent, a binder, and a disintegrant.

A uniform blend includes a blend where samples taken from the powder blender have substantially the same amount of reboxetine. In some embodiments:

- when 1 sample is tested from each of 10 locations, such as 10 random locations, in the powder blender where blending occurs, the relative standard deviation (relative standard deviation=[(standard deviation)/(mean)]×100%) of the content of reboxetine for the 10 samples, is 5% or less, 4% or less, or 3% or less; or
- a) when 3 samples are tested from each of 10 locations, such as 10 random locations, in the powder blender where blending occurs, the relative standard deviation (relative standard deviation=[(standard deviation)/(mean)]×100%) of the content of reboxetine for the 10 samples, is 7% or less, 6% or less, or 5% or less;
- In some embodiments, when 10 units of a dosage form, such as 10 tablets, are tested, such as randomly tested, from a single batch, the relative standard deviation (relative standard deviation=[(standard deviation)/(mean)]×100%) of the content of reboxetine for the 10 samples, is 5% or less, 4% or less, or 3% or less.

A composition described herein may be sterilized.

Unless otherwise indicated, any reference to a compound herein, such as reboxetine, by structure, name, or any other means, includes pharmaceutically acceptable salts; alternate solid forms, such as polymorphs, solvates, hydrates, etc.; tautomers; or any other chemical species that may rapidly convert to a compound described herein under conditions in which the compounds are used as described herein.

Reboxetine has at least two polymorph forms: Polymorph 1 and Polymorph 2.

Polymorph 1 has an X-Ray powder diffractogram (XRPD) depicted in FIG. 1. The XRPD peaks that are specific to Polymorph 1 are located at (2θ): 7.63, 9.88, 11.45, 14.43, 14.73, 15.89, 17.05, 17.43, 18.04, 18.80, 19.36, and 25.80.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 7.63.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 9.88.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 11.45.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 14.43.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 14.73.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 15.89.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 17.05.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 17.43.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 18.04.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 18.80.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 19.36.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 25.80.

Polymorph 1 has a Differential Scanning calorimetry (DSC) thermogram, at a 1° C./min heating rate that is depicted in FIG. 3. The DSC thermogram has an endothermic peak at about 145° C., about 145.0° C., or about 145.00° C.

Some embodiments include a polymorph of reboxetine having DSC thermogram which has an endothermic peak at about 145° C., about 145.0° C., or about 145.00° C.

Polymorph 2 has an XRPD depicted in FIG. 2. The peaks that are specific to Polymorph 1 are located at (° 2θ): 4.71, 9.34, 11.12, 12.04, 14.01, 14.28, 15.48, 16.52, 16.79, 17.63, 18.13, 18.40, 19.44, 19.78, 20.65, 24.15, and 26.72.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 4.71.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 9.34.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 11.12.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 12.04.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 14.01.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 14.28.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 15.48.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 16.52.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 16.79.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 17.63.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 18.13.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 18.40.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 19.44.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 19.78.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 20.65.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 24.15.

Some embodiments include a polymorph of reboxetine having an XRPD peak located at a position (° 2θ) of 26.72.

Polymorph 2 has a DSC thermogram, at a 1° C./min heating rate that is depicted in FIG. 4. The DSC thermogram has an endothermic peak at about 148° C., about 147.9° C., or about 147.85° C.

Some embodiments include a polymorph of reboxetine having DSC thermogram which has an endothermic peak at about 148° C., about 147.9° C., or about 147.85° C.

Some dosage forms containing reboxetine may contain unacceptable levels of nitroso impurities. 2-((2-Ethoxyphenoxy) (phenyl)methyl)-4-nitrosomorpholine below may be used to determine the quality of a pharmaceutical composition comprising reboxetine. For example, a sample of a dosage form may be analyzed using a chromatographic method, such as high-performance liquid chromatography (HPLC) or gas chromatography (GC). A sample of 2-((2-ethoxyphenoxy) (phenyl)methyl)-4-nitrosomorpholine may also be analyzed using a chromatographic method, such as HPLC or GC. This may be useful, for example, for determining the retention time of nitroso impurities, and for determining the sensitivity of the detector or a chromatographic instrument to a nitroso compound. Thus, one method may comprise comparing a chromatographic result obtained from the pharmaceutical composition to a chromatographic result obtained from 2-((2-ethoxyphenoxy) (phenyl)methyl)-4-nitrosomorpholine.

[Image Omitted]

In some embodiments, a pharmaceutical composition or a dosage form may contain less than 15 ppm of 2-((2-ethoxyphenoxy) (phenyl)methyl)-4-nitrosomorpholine, such as less than 13 ppm, about 0.5-13 ppm, about 2-5 ppm, about 0.5-2 ppm, about 2-3 ppm, about 3-4 ppm, about 4-5 ppm, about 5-6 ppm, about 6-8 ppm, about 8-10 ppm, or about 10-13 ppm, of 2-((2-ethoxyphenoxy) (phenyl)methyl)-4-nitrosomorpholine.

The terms “treating” or “treatment” broadly includes any kind of treatment activity, including the diagnosis, cure, mitigation, or prevention of disease in man or other animals, or any activity that otherwise affects the structure or any function of the body of man or other animals. In some embodiments, the mammal being treated is a human being. In some embodiments, the mammal being treated is a non-human mammal, such as a dog, a cat, a mouse, a rat, a rabbit, a monkey, a horse, a pig, etc.

A composition described herein may be used to treat a condition such as a nervous system disorder, including an addictive disorder (including those due to alcohol, nicotine, and other psychoactive substances), a withdrawal syndrome, an adjustment disorder (including depressed mood, anxiety, mixed anxiety and depressed mood, disturbance of conduct, and mixed disturbance of conduct and mood), depression (including major depressive disorder, alone or in combination with other antidepressants), an age-associated learning or mental disorder (including Alzheimer's disease), anorexia nervosa apathy, an attention-deficit (or another cognitive) disorder due to general medical conditions, attention-deficit hyperactivity disorder (ADHD), bipolar disorder, bulimia nervosa, chronic fatigue syndrome, chronic or acute stress, chronic pain, conduct disorder, cyclothymic disorder, depression (including adolescent depression and minor depression), dysthymic disorder, fibromyalgia and other somatoform disorders (including somatization disorder, conversion disorder, pain disorder, hypochondriaism, body dysmorphic disorder, undifferentiated somatoform disorder, and somatoform NOS), generalized anxiety disorder (GAD), incontinence (i.e., stress incontinence, genuine stress incontinence, and mixed incontinence), stress urinary incontinence, an inhalation disorder, an intoxication disorders (alcohol addiction), mania, migraine headaches, obesity (e.g., reducing the weight of obese or overweight patients), an obsessive compulsive disorder or a related spectrum disorder, oppositional defiant disorder, panic disorder, peripheral neuropathy, post-traumatic stress disorder, premenstrual dysphoric disorder (i.e., premenstrual syndrome and late luteal phase dysphoric disorder), a psychotic disorder (including schizophrenia, negative symptoms of schizophrenia, schizoaffective or schizophreniform disorder, either alone or as an adjuvant therapy), seasonal affective disorder, a sleep disorder (such as narcolepsy, including narcolepsy with cataplexy, or enuresis), social phobia (including social anxiety disorder), a specific developmental disorder, selective serotonin reuptake inhibition (SSRI) “poop out” syndrome (i.e., wherein a patient who fails to maintain a satisfactory response to SSRI therapy after an initial period of satisfactory response), TIC disorders (e.g., Tourette's Disease), post-shingles pain, painful diabetic peripheral neuropathy, postherpetic neuralgia, syncope, and/or vasovagal syncope, etc.